Remdesivir - Gilead Sciences
Alternative Names: Captisol-enabled remdesivir; Captisol®-enabled GS 5734; GS-5734; Redyx; VEKLURY; VekluryLatest Information Update: 07 Feb 2024
At a glance
- Originator Gilead Sciences
- Developer Capital Medical University; China-Japan Friendship Hospital; Chinese Academy of Medical Sciences; Dr Reddys Laboratories; Gilead Sciences; INSERM; National Institute of Allergy and Infectious Diseases; NeuroActiva; Roche
- Class Adenine nucleotides; Amines; Antivirals; Esters; Furans; Nitriles; Phosphorus compounds; Pyridazines; Pyrroles; Small molecules; Triazines
- Mechanism of Action RNA replicase inhibitors
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Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- Marketed COVID 2019 infections
- Phase III COVID-19 pneumonia
- Phase II Ebola virus infections
- No development reported Neurological disorders
Most Recent Events
- 11 Oct 2023 Efficacy data from a phase III REDPINE trial in Covid-19 infections presented at the IDWeek 2023 (IDW-2023)
- 11 Oct 2023 Pooled adverse events data from a phase III ACTT-1 trial, phase III PINETREE trial, phase III REDPINE trial presented at the IDWeek 2023 (IDW-2023)
- 19 Sep 2023 European Medicines Agency (EMA) grants positive opinion to extend the use of remdesivir to treat people with COVID-2019 infections (with mild to severe hepatic impairment)
Development Overview
Introduction
Remdesivir (GS 5734) is a small molecule, monophosphoramidate prodrug of adenosine triphosphate analogue being developed by Gilead Sciences for the treatment of viral infections, including COVID-2019 infections, COVID-19 pneumonia, SARS-COV-2 acute respiratory disease, and Ebola virus infections. An inhaled nanopartical formulation of the drug is being developed for the treatment of neurological disorders and COVID-2019 infections. Upon administration, remdesivir is metabolised into a nucleoside monophosphate intermediate, which is subsequently phosphorylated by cellular kinases to form the pharmacologically active nucleoside triphosphate metabolite (GS 443902). GS 441524 is the predominant circulating metabolite of remdesivir. Remdesivir triphosphate (RDV-TP) acts as an analogue of adenosine triphosphate (ATP) and competes with ATP for incorporation into RNA and inhibits the action of viral RNA-dependent RNA polymerase (also known as RNA-replicase). This results in the termination of RNA transcription and decreases viral RNA production. Remdesivir is launched in the US and Egypt for the treatment of COVID-2019 infections. Remdesivir is approved in Japan, United Arab Emirates, US and conditionally approved in Taiwan and Singapore for the treatment of COVID-2019 infections. The drug is also approved on conditional basis in the EU, Iceland, Norway and Liechtenstein for the treatment of COVID-2019 infections and has been granted provisional approval in Australia, for the treatment of COVID-2019 infections. In India, remdesivir is approved for emergency restricted use. The product is available globally on a compassionate basis for the same indication. The drug is under review in European Union for the treatment of pediatric patients of under age 12. Clinical development of remdesivir is underway for the treatment of COVID-2019 infections and COVID-19 pneumonia in multiple countries. Clinical development of the intravenous formulation is underway for the treatment of Ebola virus infections in Congo, Guinea, Liberia and the US. Clinical development of the inhaled nanopartical formulation is ongoing in the US.
The Drug Controller General of India (DCGI) granted regulatory approval to Jubilant Life Sciences, for restricted emergency use of generic version of remdesivir, called JUBI-R, for the treatment of COVID-2019 infections, in July 2020. The drug will be available by the first week of August 2020 [1] .
The DCGI granted regulatory approval to Mylan (now Viatris), for restricted emergency use of generic version of remdesivir lyophilised powder for injection called DESREM™ for the treatment of COVID-2019 infections, in July 2020 [2] .
The DCGI granted regulatory approval to Hetero, for use of generic version of remdesivir, called COVIFOR (injectable vial) in India., for the treatment of COVID-2019 infections, in June 2020. The product is launched under a licensing agreement with Gilead Sciences [3] .
The DCGI granted regulatory approval to Cipla, for restricted emergency use of generic version of remdesivir called CIPREMI for the treatment of COVID-2019 infections, in June 2020 [4] .
In November 2020, Upjohn was merged with Mylan to form Viatris [5] .
In May 2021, NeuroRx was merged with Big Rock Partners to form NRx Pharmaceuticals [6] .
As at April 2023, no recent reports of development had been identified for clinical-Phase-Unknown development in COVID-2019-infections in Israel (IV, Infusion).
As at August 2023, no recent reports of development had been identified for phase-I development in COVID-2019-infections (Combination therapy, In volunteers) in USA (Inhalation), phase-I development in Neurological-disorders (Combination therapy, In volunteers) in USA (Inhalation), phase-I development in Neurological-disorders (Monotherapy, In volunteers) in USA (Inhalation).
Company Agreements
In July 2022, Gilead Sciences and the European Commission signed a new joint procurement agreement (JPA) to ensure continued rapid and equitable access to remdesivir for participating Member States across the European Union (EU) and European Economic Area (EEA). The agreement covers purchases of remdesivir over the next twelve months and has the option to be extended for an additional six months. [7]
In May 2020, Gilead Sciences entered into a worldwide collaboration agreement with Mylan (now Viatris) to expand access to the investigational antiviral remdesivir for the treatment of COVID-2019 infections. Under the terms of agreement, Mylan has licensed the non-exclusive rights to manufacture and distribute remdesivir in 127 low- and middle-income countries, including India. [8] [5]
In October 2020, Gilead reported that it will be responsible for distributing remdesivir (Veklury®) in the United States, since 1st October 2020. Remdesivir distribution has transitioned from the US Government to Gilead. AmerisourceBergen will continue to serve as the sole US distributor of Veklury through the end of 2020 and will sell the product directly to hospitals. [9]
In August 2020, Pfizer entered into an agreement with Gilead Sciences to manufacture and supply Gilead’s investigational antiviral remdesivir, as one of multiple external manufacturing organizations supporting efforts to scale up supply of the investigational treatment for COVID-19. Under the terms of the agreement, Pfizer will provide contract manufacturing services at Pfizer’s McPherson, Kansas facility to manufacture and supply remdesivir for Gilead [10]
In May 2020, Gilead Sciences entered into a non-exclusive licensing agreement with Jubilant Life Sciences, for the approval, manufacture and distribution of remdesivir, for the treatment of COVID-19 infections. Under the terms of this agreement, Jubilant will manufacture the API and Finished product at a commercial scale and market it in 127 countries, including India. In addition, Jubilant has the right to receive the technology transfer of the Gilead manufacturing process, so as to scale up production. [1] [11]
In June 2020, Gilead Sciences entered into a non-excusive licensing agreement with Dr. Reddy's Laboratories for manufacturing and marketing of remdesivir. Under the terms of the agreement, Dr. Reddy's will register, manufacture and sell remdesivir, in 127 countries including India. Dr Reddy’s will receive technology transfer from Gilead for manufacturing of this drug [12]
In June 2020, Zydus Cadila, entered into a non-exclusive licensing agreement with Gilead Sciences for the manufacturing and distribution of remdesivir for the treatment of COVID-2019 infections. Under the terms of the agreement, Zydus will receive the manufacturing know-how from Gilead Sciences to manufacture the API for remdesivir and finished product and market it in 127 countries including India. The license is royalty free until another pharmaceutical product or vaccine is approved for the treatment or prevention of COVID 2019 by the US FDA or EMA or the WHO announcing the end of the public health emergency. Zydus will leverage its ability to scale up production to reach patients across India and across the 127 countries in Gilead’s Global Patient Solution region. [13]
In May 2020, Gilead Sciences entered into a non-exclusive licensing agreement with Cipla for the manufacturing and distribution of remdesivir for the treatment of COVID-19 infections. Under the terms of this agreement, Cipla will manufacture the API and Finished product at a commercial scale and market it in 127 countries including India and South Africa under Cipla's own brand name. In addition, Cipla will receive the manufacturing know-how from Gilead Sciences. [14]
In May 2020, Hetero and Gilead Sciences entered into a licensing agreement for the manufacturing and distribution of remdesivir for the treatment of COVID-19 infections. Under the terms of the agreement, Hetero can supply remdesivir in 127 countries including India, subjective to regulatory approvals in respective countries. [15]
In February 2020, Ligand Pharmaceuticals entered into a supply agreement of Captisol with Double-Crane Pharmaceuticals. As per the terms , Ligand Pharmaceuticals will supply Captisol to Double Crane for use in preclinical and clinical studies of remdesivir to treat COVID-19 infections. Ligand Pharmaceuticals will receive revenues based on the amount of Captisol ordered by Double Crane. [16]
Ligand Pharmaceuticals in May 2020, entered into a supply agreement of Captisol with OnKure Therapeutics for use in clinical studies of remdesivir to treat COVID-19 infections. [16]
As at April 2020, Ligand under a supply agreement is supplying Captisol to Gilead Sciences to evaluate remdesivir in clinical trials for the treatment for COVID-2019 infections. Earlier, in December 2015, Gilead Sciences entered into a supply agreement with Ligand Pharmaceuticals for the supply of Captisol® to Gilead for use in a Captisol®-enabled program directed against Ebola virus disease including remdesivir, and in such other programs, if the companies intend to expand the agreement. Under the terms of the agreement, Ligand will receive an upfront Drug Master File reference fee, and it is also eligible to receive commercial revenue from the shipment of Captisol to Gilead (Ligand Pharmaceuticals, Form 10-K, December 2015). [17]
Key Development Milestones
COVID-2019 infections and COVID-19 pneumonia
In September 2023, Gilead Sciences announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) granted a positive opinion for the use of Veklury® (remdesivir) to treat people with COVID-19 with mild to severe hepatic impairment. The European Commission (EC) will review the CHMP recommendation. This positive opinion was based on results from a phase I trial of safety and pharmacokinetics in people with hepatic impairment (GS-US-540-9014). Based upon these results, the revised recommendation requires no dose adjustment or liver function testing before or during treatment with Veklury [18] .
In August 2023, Gilead Sciences announced that the US FDA approved a supplemental new drug application (sNDA) for the use of Veklury® (remdesivir) with no dose adjustments to treat COVID-19 in people with mild, moderate and severe hepatic impairment. The approval is based on results from a phase I GS-US-540-9014 trial [see below] [19] .In August 2023, remdesivir (Veklury®) received US FDA and European Commission (EC) approval to extend the use of Veklury to treat COVID-19 in people with severe renal impairment, including those on dialysis [20] . In July 2023, the US FDA approved supplemental new drug application (sNDA) for remdesivir (Veklury®) injection for the treatment of COVID-2019 infection in patients with severe renal impairment and including patients on dialysis in the US. This approval for use in patients with severe renal impairment was based on results from a phase I trial and phase III REDPINE trial [see below] [21] .
In September, Therapeutic Goods Administration (TGA), Australia granted provisional approval to remdesivir (Veklury) to extend the use of the COVID-19 treatment in adults and paediatric patients (at least 4 weeks of age and weighing at least 3 kg) who have pneumonia due to SARS-CoV-2, who require supplemental oxygen, and adults and paediatric patients (weighing at least 40 kg) who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Previously in July 2020, TGA had granted approval to Gilead Sciences for the use of VEKLURY in adults and adolescents aged 12 years and older (and weighing at least 40 kg) with pneumonia who have been hospitalised and require oxygen. The TGA approval decision was based on results from the CARAVAN study, a Phase II/III trial and the PINETREE trial, a Phase III study [see below] [22] .
In April 2022, the US FDA approved remdesivir (Veklury®) injection for the treatment of COVID-2019 infection in pediatric patients 28 days of age and older weighing at least 3 kilograms (about 7 pounds) with positive results of direct SARS-CoV-2 viral testing, who are hospitalised, or not hospitalised and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalisation or death. As a result of this approval, the agency also revoked the emergency use authorisation for Veklury that previously covered this pediatric population. The approval is supported by the efficacy results from phase III clinical trials in adults and is also supported by a phase II/III, single-arm, open-label clinical study of 53 pediatric patients at least 28 days of age and weighing at least 3 kilograms (about 7 pounds) with confirmed SARS-CoV-2 infection and mild, moderate or severe COVID-19 [23] .
In October 2020, US FDA approved remdesivir (Veklury®) for the treatment of COVID-2019 infection in patients (12 years of age and older and weighing at least 40 kilograms) requiring hospitalization, and subsequently launched the product in the US. The FDA granted this application Fast Track and Priority Review designations. The Agency also granted this application a Material Threat Medical Countermeasure Priority Review Voucher, which provides additional incentives for certain medical products intended to treat or prevent harm from specific chemical, biological, radiological and nuclear threats [24] [25] [26] . In August 2020, Gilead completed the submission of a rolling NDA to the US FDA, seeking approval for usage of remdesivir (Veklury®), for the treatment of patients with COVID-2019 infections. The completion of this filing constituted the final tier of the submission, that was initiated in April 2020. The filing was supported by data from two phase III company-conducted drug trials, along with a phase III study conducted by National Institute of Allergy and Infectious Diseases (NIAID) [see below]. Drug treatment in these studies manifested faster recovery times relative to placebo, with comparable clinical improvements witnessed with both 5-day or 10-day treatment duration. Both treatment groups were reflective of a well-tolerated safety profile for the drug, bereft of new safety signals [27] .
In January 2022, the US FDA expanded the pediatric Emergency Use Authorization (EUA) of remdesivir to include non-hospitalized pediatric patients younger than 12 years of age who are at high risk of disease progression. The US FDA EUA approval decision was based on results from the PINETREE phase III trial (see below) [28] .
In October 2020, the US FDA revised the Emergency Use Authorization (EUA) for remdesivir to remove the uses that are approved under Gilead’s New Drug Application (NDA). Thus, the EUA for Veklury continues to authorize Veklury for emergency use by licensed healthcare providers for the treatment of suspected or laboratory-confirmed COVID-19 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg. In August 2020, the US FDA expanded the scope of the emergency use authorization for remdesivir to include treatment of hospitalised adult and paediatric patients with suspected or laboratory-confirmed COVID-19, irrespective of their severity of disease, regardless of the need for supplemental oxygen. Earlier, in May 2020, the US Food and Drug Administration (FDA) granted an emergency use authoristion to remdesivir for the treatment of suspected or laboratory-confirmed severe COVID-19 infections in adults and children with low blood oxygen levels or needing oxygen therapy or more intensive breathing support such as a mechanical ventilator. The drug is administered via intravenous infusion and is supplied either as an injection, 100mg, lyophilised powder, or as an injection, 100mg/20 mL (5mg/mL), concentrated solution [29] [30] [9] [31] [32] .
In September 2020, Dr Reddy's Laboratories announced the launch of remdesivir for restricted emergency use, under a brand name Redyx® in India for the treatment of COVID-2019 infections. The Drug Controller General of India (DCGI) granted regulatory approval for restricted emergency use to remdesivir, for the treatment of suspected or laboratory confirmed COVID-2019 infections in adults and children hospitalised with severe disease in June 2020 [33] [34] [35] .
In May 2023, Gilead Sciences announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) granted a positive opinion for the use of remdesivir (Veklury®) in COVID-2019 patients with severe renal impairment, including those on dialysis. The European Commission (EC) will review the CHMP recommendation and, if adopted, remdesivir will become the first and only authorized antiviral COVID-19 treatment that can be used across all stages of renal disease. The positive opinion was based on the results from a phase I pharmacokinetic study (GS-US-540-9015), as well as results from the phase III REDPINE trial [see below] that evaluated the safety of remdesivir in patients hospitalized for COVID-19 with severe renal impairment [36] .
In September 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion to extend the indication of remdesivir (Veklury®) for the treatment of pediatric patients (under 12 years of age ) (weighing at least 40 kg) who do not require supplemental oxygen and are at increased risk of progressing to severe COVID-19 and pediatric patients (4 weeks of age and older and weighing at least 3 kg) with SARS-CoV-2 with pneumonia who require supplemental oxygen (low- or high-flow oxygen or other non-invasive ventilation at the start of treatment) [37] . In July 2022, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion on the fulfillment of the last specific obligation and recommended the granting of Marketing Authorization (MA) for Veklury® (remdesivir) that is no longer subject to specific obligations [38] . As of December 2021, Gilead Sciences reported that the European Commission (EC) has approved a variation to the Conditional Marketing Authorization for remdesivir (Veklury®) to include adults who do not require supplemental oxygen and are at an increased risk of progressing to severe COVID-19. This decision follows the positive recommendation of the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), to expand the indication for remdesivir. The decision was supported by results from a phase III CARAVAN trial [see below]. This expanded indication in the EU adds to the previous Conditional Marketing Authorization of remdesivir enabling the treatment of COVID-19 in adults and adolescents (aged 12 to less than 18 years and weighing at least 40 kg) with pneumonia requiring supplemental oxygen [39] . Earlier, In May 2021, the CHMP recommended the renewal of the conditional marketing authorisation for remdesivir (Veklury®), which was granted in July 2020 by the European Commission for the treatment of COVID-2019 infections in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen [40] . Earlier, in June 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency's (EMA) adopted a positive opinion recommending the granting a conditional marketing authorisation (CMA) to remdesivir. The company will have to submit the final reports of the remdesivir studies to the Agency by December 2020, and further data on the quality of the medicine, as well as the final data on mortality, by August 2020. However, in October 2020, EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) initiated the review of a safety signal to assess the reports of acute kidney injury in few patients who were administered remdesivir for the treatment of COVID-2019 infections. The outcome of the PRAC’s review will be communicated after reviewing any new information that is available through monthly summary safety reports, periodic safety update reports, and signal detection [41] . Previously in June 2020, the EMA had received an application for CMA of remdesivir and had formally started its evaluation. At the conclusion of the first cycle of the rolling review in May 2020, the CHMP invited the company to submit further data together with an application for a conditional marketing authorisation. Also, EMA’s committee for medicines for children (PDCO) rapidly issued its opinion on the company’s paediatric investigation plan (PIP). Earlier, the CHMP started a rolling review of data on the use of remdesivir based on preliminary results from the NIAID- ACTT study [see below], which suggested a beneficial effect of remdesivir in the treatment of hospitalised patients with mild-to-moderate or severe COVID-2019 infections [42] [43] [44] [45] .
As of July 2020, the United Arab Emirates’ Ministry of Health and Prevention approved remdesivir for the treatment of patients with COVID-2019 infections [42] .
In June 2020, the US FDA reported that it is revising fact sheet for health care providers to state that administration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir. However, US FDA is not aware of any instances of reduced activity occurring in clinical setting and it will continue to evaluate all the data related to remdesivir. The FDA has also revised the fact sheet for health care providers to clarify dosing and administration recommendations and to provide additional safety data and supporting data from clinical trials [46] .
In June 2020, The Health Sciences Authority (HSA), in consultation with its Medicines Advisory Committee, granted conditional approval for remdesivir. As part of the conditional approval, Gilead is required to collect the relevant safety data and to monitor the use of remdesivir. HSA will also require data from ongoing clinical studies to be submitted post-approval to ensure the continued safety and efficacy of the product. Earlier in March 2020, HSA initiated an early access of remdesivir to COVID-19 patients in Singapore through the expeditious evaluation and approval of its use in clinical trials. Gilead filed for registration of remdesivir in Singapore in May 2020 [47] .
In June 2020, the Taiwan Food and Drug Administration (TFDA) of the Ministry of Health and Welfare (MOHW) conditionally approved remdesivir for patients with severe SARS-CoV-2 infection, according to the Article 48-2 of Pharmaceutical Affairs Act, provided that the pharmaceutical company would implement a risk management plan (RMP) to ensure the safety after the importation. Earlier in May 2020, TFDA hold a meeting and invited pharmaceutical and clinical experts to discuss the application and approval requirements of remdesivir [48] .
In May 2020, Gilead Sciences announced that Japanese Ministry of Health (MHLW) has granted regulatory approval of Venklury® (remdesivir) as a treatment for COVID-2019 infections under an exceptional approval pathway. The exceptional approval was granted due to the COVID-19 pandemic and references the Emergency Use Authorization of remdesivir in the US. The approval was granted on the basis of clinical data obtained from the phase III SIMPLE trial (see below) and from Gilead's compassionate use program, that included patients from Japan [49] .
As of February 2021, remdesivir is available in Egypt (NCT04738045).
In January 2022, Gilead Sciences reported that the US FDA granted expedited approval of a supplemental new drug application (sNDA) for remdesivir (Veklury) for the treatment of non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19, including hospitalization or death. This approval expands the role of Veklury, which is the antiviral standard of care for the treatment of patients hospitalized with COVID-19. The expanded indication allows for remdesivir to be administered in qualified outpatient settings that can administer daily intravenous (IV) infusions over three consecutive days. The US FDA sNDA approval decision was based on results from the PINETREE phase III trial (see below) [28] Earlier, in October 2021, Gilead Sciences submitted sNDA for remdesivir for the treatment of COVID-19 infections in an outpatient setting [50] .
In September 2022, WHO Expands Recommendation for Remdesivir (Veklury®) in severe COVID-2019 infections and continues to conditionally recommend Veklury in those with non-severe COVID-19 at the highest risk of hospitalization [51] .
In March 2020, the US FDA granted orphan drug designation to remdesivir for the treatment of of COVID-2019 infections. However the status was withdrawn by the US FDA in the same month following submission of a request by Gilead to the US FDA to rescind the orphan drug designation [52] [53] [54] .
In November 2022, NeuroRx in collaboration with National Institute of Allergy and Infectious Diseases (NIAID), International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), University of Copenhagen, Medical Research Council, Kirby Institute, Washington D.C. Veterans Affairs Medical Center, AIDS Clinical Trials Group, National Heart, Lung, and Blood Institute (NHLBI), US Department of Veterans Affairs, Prevention and Early Treatment of Acute Lung Injury (PETAL), Cardiothoracic Surgical Trials Network (CTSN), and Gilead Sciences completed the phase III TESICO trial to assess the safety and effectiveness of aviptadil [see ADIS Insight drug profile800002016] and remdesivir in treating hospitalized COVID-19 patients, and patients with acute respiratory failure (ACTIV-3b; NCT04843761). The multicenter, adaptive, randomized, blinded control trial was initiated in April 2021 and enrolled 473 patients in the US. The first patient was dosed in the same month [55] [56] . Previously, in April 2021, NeuroRx had reported that aviptadil has been identified by the National Institutes of Health (NIH) as one of two drugs selected for inclusion in a planned phase III TESICO (Therapeutics for Severely Ill Inpatients with COVID-19), multicenter clinical trial that will include the US and multiple foreign countries. The trial is funded by the US Government COVID-19 Therapeutics Response and sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). NeuroRx reported that TESICO protocol has been reviewed and approved as a phase III trial by the US FDA [57] . In April 2021, NeuroRx was actively collaborating with NIH to provide remediated formulation and stability data to European and South American Regulatory Authorities so that NIH can extend TESICO trial to Europe [58] .
In October 2023, pooled safety data of three phase III trials (phase III ACTT-1 trial, phase III PINETREE trial, phase III REDPINE trial) in COVID-2019 infections was presented at the IDWeek 2023 (IDW-2023) [59] .
In June 2022, Gilead Sciences terminated the phase III REDPINE trial of remdesivir due to study enrollment feasibility and the decision was not based on efficacy or safety concerns (NCT04745351; GS-US-540-5912; EudraCT2020-005416-22). The trial was initiated in March 2021 to evaluate the efficacy and safety of remdesivir in patients with severely reduced kidney function who are hospitalised for COVID-2019 infections. The randomised, double-blind, placebo-controlled, parallel-group study enrolled 249 patients in the US, Brazil, Portugal, South Africa, Spain and the UK [60] . In February 2023, company presented data from the trial at 30th Conference on Retroviruses and Opportunistic Infections (CORI-2023) [61] . In October 2023, Gilead Sciences presented efficacy data from phase III REDPINE trial in COVID-2019 infections at the IDWeek 2023 (IDW-2023) [62] .
In February 2021, Daewoong Pharmaceutical initiated a phase III trial to evaluate the efficacy and safety of oral Camostat mesylate (DWJ1248) [see Adis Insight Drug profile [63] ] treatment along with remdesivir (IV) in severe COVID-19 patients (NCT04713176; DW_DWJ1248302). The double-blind, randomised, placebo-controlled, multi-center trial intends to enroll approximately 1022 participants in South Korea [64] .
In October 2020, the University of Minnesota, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institutes of Health (NIH), initiated a phase III ITAC trial to evaluate the safety, tolerability and efficacy of anti-coronavirus hyperimmune intravenous immunoglobulin (hIVIG) versus placebo, along with remdesivir as standard of care, in adult patients hospitalised for COVID-19 and have had symptoms for 12 days or fewer without life-threatening organ dysfunction or end-organ failure (INSIGHT013; EudraCT2020-002542-16; INSIGHT 013; NCT04546581). The Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) trial is a double-blind, placebo-controlled, randomised, adaptive and enrolling approximately 500 patients in the US, Mexico and 16 other countries in Africa, Asia, Europe, North America and South America. The primary outcome of the trial is to compare the health status of participants in each group on day seven, based on an ordinal outcome with seven mutually exclusive categories ranging from no limiting symptoms due to COVID-19, to death [65] . Emergent BioSolutions [see adis profile 800057829] , Grifols [see adis profile 800057941] and, CSL Behring with Takeda [see adis profile 800057734] will provide anti-coronavirus hIVIG for the trial. In October 2020, NIAID announced that primary analysis was planned after all participants finish 28 days of follow-up. An independent data and safety monitoring board (DSMB) will review interim safety and efficacy data to ensure patient well-being and safety as well as study integrity [66] . In April 2021, Takeda announced that, top-line data from this trial demonstrated that the trial did not met its endpoint. However, no safety signals were observed [67] .
In April 2021, Gilead Sciences announced the termination of the PINETREE phase III trial designed to evaluate the efficacy of remdesivir (RDV) in reducing the rate of hospitalisation or death in non-hospitalised participants with early stage coronavirus disease 2019 (COVID-19) and to evaluate the safety of RDV administered in an outpatient setting (NCT04501952; EudraCT-2020-003510-12; GS-US-540-9012). The trial was terminated due to study enrollment feasibility and changing needs of non-hospitalised patients. The decision to terminate the trial was not due to efficacy or safety concerns. Patients already enrolled in the study will continue to be followed and the study will remain blinded [68] . The randomised trial was initiated in September 2020 and planned to enroll about 1,200 patients, but by late spring, the availability of monoclonal antibodies and vaccines made it difficult to find eligible patients, so the trial was stopped and analyzed with 584 participating patients in the US, UK, Portugal, Denmark and Spain. In September 2021, Gilead Sciences released efficacy and safety data from a phase III trial. In the same month, the company released new data at ID Week 2021 (IDW-2021) [69] . In December 2021, Intermountain Healthcare released data from the trial [70] [71] [72] [73] .
In August 2020, National Institute of Allergy and Infectious Diseases (NIAID) initiated the phase III ACTT-3 trial to evaluate safety and efficacy of remdesivir with interferon beta-1a [see Adis Insight drug profile 800007022] in patients with COVID-2019 infection (NCT04492475; 20-0006 ACTT-3). The randomised, double-blind trial intends to enrol approximately 1 038 adults and the elderly patients in the US, Japan, South Korea, Mexico and Singapore [74] . In September 2020, National Institute of Allergy and Infectious Diseases announced that the trial will no longer recruit severely ill COVID-19 patients after an interim review of 266 patients safety data by Data and Safety Monitoring Board (DSMB), however the study will continue to enrol hospitalised patients on low-flow oxygen and those not requiring supplemental oxygen. In October 2020, NIAID disclosed that in hospitalised patients with COVID-19 and lower respiratory tract involvement who received remdesivir had a statistically significant shorter time to recovery compared to patients who received placebo [75] [66] .
In March 2021, Genentech announced that the phase III REMDACTA trial did not meet its primary endpoint, measured by improved time to hospital discharge up to day 28 in patients with severe COVID-19 pneumonia receiving standard of care. REMDACTA did not meet key secondary endpoints, which included likelihood of death, likelihood of progression to mechanical ventilation or death, and clinical status. No new safety signals were identified for tocilizumab in the REMDACTA trial [76] . In May 2020, Roche in collaboration with Gilead Sciences initiated the phase III REMDACTA trial to evaluate the safety and efficacy of tocilizumab [see Adis Insight drug profile 800010359] plus remdesivir, versus placebo plus remdesivir in hospitalised patients with severe COVID-19 pneumonia (WA42511; EudraCT2020-002275-34; NCT04409262). The randomised, double-blind trial intends to enroll approximately 450 patients in the US, Canada, Spain, Russia and Brazil [77] [78] .
As of September 2021, Institut National de la Santé Et de la Recherche Médicale (INSERM) discontinued treatment with remdesivir in the phase III DisCoVeRy trial designed to assess safety and efficacy of remdesivir and other therapeutics including hydroxychloroquine, lopinavir/ritonavir compared with standard of care, based on analyses review by both independent data and safety monitoring board (DSMC/DSMB), the Solidarity Executive Group and the DisCoVeRy steering committee (NCT04315948; C20-15; EudraCT2020-000936-23). Institut National de la Santé Et de la Recherche Médicale (INSERM) and Gilead Sciences initiated the trial in March 2020. The primary endpoint of study was to determine the percentage of patients reporting each severity rating on a 7-point ordinal scale in 15 days. The randomised, adaptive trial intended to enrol approximately 3300 patients in France, Luxembourg, Austria, Belgium, Norway and Portugal [79] [80] .
In June 2020, Gilead Sciences completed the first phase III SIMPLE trials that evaluated the safety and efficacy of both a 5-day and a 10-day dosing regimen of remdesivir administered intravenously in patients with severe manifestations of COVID-19 (NCT04292899; GS-US-540-5773; EudraCT2020-000841-15; SIMPLE-severe). The trial was initiated in March 2020 and recruited 4891 patients globally including Germany, Spain, Italy, the Netherlands, the UK, Sweden, the US, Hong Kong, South Korea, Singapore, China, Taiwan, France, Japan and Switzerland. In April 2020, the company reported that the study was stopped in patients with severe symptoms due to delayed enrollment. However in June 2020, Gilead announce addition of expansion phase of the study was added to enroll up to 5 600 additional patients, including those on mechanical ventilation. In April 2020, efficacy and safety data from the trial was released by Gilead Sciences. In May 2020, Gilead announced that the data from the SIMPLE-Severe study support treatment of some patients for 5 days rather than 10 days, depending on clinical status. In July 2020, efficacy data from the trial were released by Gilead Sciences. In October 2020, updated efficacy data from the trial were presented at the IDWeek 2020 (IDW-2020) [81] [82] [83] [84] [79] [85] [86] [87] .
In June 2020, Gilead Sciences completed the second SIMPLE trial that evaluated the safety and efficacy of a 5-day and a 10-day dosing regimen of remdesivir administered intravenously in patients with moderate manifestations of COVID-19, compared with standard of care (NCT04292730; GS-US-540-5774; EudraCT2020-000842-32; SIMPLE-moderate) . The trial enrolled 1113 patients . Previously in April 2020, Gilead sciencs announced that the trail met its primary endpoint in China, France, Germany, Hong Kong, Iran, Italy, Japan, Netherlands, Scotland, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, USA. Gilead Sciences has donated remdesivir and provided scientific input for these studies. In June 2020, Gilead Sciences release data from the trial [84] [88] [89] [90] . In August 2020, updated results from the trial were released by the company [30] .
In October 2020, Gilead Sciences released final results and reported that the phase III ACTT-1 trial met its primary endpoint, demonstrating remdesivir plus standard of care was superior in shortening the time to recovery through Day 29 compared with placebo plus standard of care. The key secondary study endpoint of clinical status at Day 15 was also met [91] . In May 2020, National Institute of Allergy and Infectious Diseases completed the phase III ACTT-1 trial (Adaptive COVID-19 Treatment Trial) that evaluated the safety and efficacy of remdesivir for the treatment of COVID-2019 infections (ACTT; 20-0006; U1111-1249-9599; EudraCT2020-001052-18; NCT04280705). The randomised, double-blind, placebo-controlled trial was initiated in February 2020 and enrolled 1062 hospitalised patients in the US, Denmark, Germany, Greece, South Korea, Japan, Mexico, Singapore, Spain and the UK. In April 2020, EvergreenHealth reported initial preliminary reports from the trial. In May 2020, Gilead announced that the trial findings support the use of remdesivir with the largest benefit observed among individuals who required oxygen supplementation but were not mechanically ventilated. In June 2020, the EMA released the efficacy data from the trial [43] [92] [86] [93] . In August 2020, updated results from the trial were released by the company. As of October 2020, Gilead announced that remdesivir significantly improved time to recovery and also reduced the likelihood of disease progression [30] [9] .
In September 2020, the phase III ACTT-2 trial met the primary endpoint of reduction of time to recovery with oral baricitinib and remdesivir combination therapy, in hospitalised patients with COVID-2019 infections, when compared with remdesivir. In July 2020, National Institute of Allergy and Infectious Diseases (NIAID) completed the phase III ACTT-2 trial designed to assess the safety and efficacy of oral baricitinib and remdesivir combination therapy for the treatment of COVID-19 in hospitalized adults (ACTT-2) (20-0006ACTT2; NCT04401579). The randomised, double blind trial, initiated in May 2020, completed enrolment of 1 033 patients in the US, Japan, Denmark, South Korea, Mexico, Singapore, Spain, the UK [94] [95] [96] [94] .
In April 2020, Capital Medical University, Chinese Academy of Medical Sciences, China-Japan Friendship Hospital and Gilead Sciences suspended the randomised, controlled, double blind phase III CAP-China remdesivir 1 trial, as the epidemic of COVID-2019 was well-controlled, and no eligible patients could be recruited further (NCT04252664; CAP-China remdesivir 1). The trial evaluated the efficacy and safety of remdesivir in patients hospitalised with mild or moderate COVID-2019 infections. Patients were randomised 1:1:1 to receive up to 5 days or 10 days of remdesivir with standard of care or standard of care alone. The trial was initiated in February 2020 and enrolled 584 patients in China [97] . In October 2020, Gilead Sciences presented the results of this trial at the IDWeek 2020 (IDW-2020) [98] [99] . In March 2021, Gilead Sciences presented results at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) demonstrating effect of remdesivir on renal function in hospitalized patients with moderate COVID-19 infections [100] .
In February 2023, Gilead Sciences completed a phase II/III CARAVAN trial which evaluated the safety, tolerability, and pharmacokinetics of remdesivir in patients with COVID-19 infections (P201-2020; GS-US540-5823; EudraCT2020-001803-17; NCT04431453). The open-label trial initiated in July 2020, enroled 59 patients, aged 0 to 18 years, in the US, the UK, Italy and Spain [101] . In March 2021, efficacy and adverse events data from a trial was presented at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [102] . In February 2022, the company presented results from the trial at the 29th Conference on Retroviruses and Opportunistic Infections (virtual CROI 2022) [103] [104] . In April 2022, the company presented updated results from the trial at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022) [105] . In September 2022, the company presented updated results from the trial at the Annual meeting of the American College of Clinical Pharmacology (ACCP-2022) [106] .
In September 2022, efficacy results from phase II/III SOLIDARITY trial were released by Gilead Sciences [51] .
In June 2021, Gilead Sciences in collaboration with World Health Organisation terminated a phase II/III WHO-SOLIDARITY-GERMANY trial that evaluated the clinical efficacy and safety of investigational therapeutics relative to the control arm among hospitalised adult patients who had COVID-19 (EudraCT2020-001549-38; NCT04575064). The open, parallel, prospective, randomised trial was initiated in June 2020 and enrolled 400 participants in Germany [107] .
In March 2020, Gilead Sciences in collaboration with World Health Organisation, initiated a phase II//III NOR-SOLIDARITY trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalised adult patients diagnosed with COVID-19. This trial will follow the core WHO protocol but has additional efficacy, safety and explorative endpoints (N-ReCOVID 19; S-ReCOVID 19; 118684; EudraCT2020-000982-18; NCT04321616; WHO-NOR-COVID19). The multicentre, open, parallel, prospective, randomised trial intends to enrol 1218 participants in Norway. The trial prematurely ended in Sweden [108] .
In March 2020, Sunnybrook Health Sciences Centre initiated the phase II Canadian Arm of the SOLIDARITY Trial (CATCO) trial to evaluate the safety and efficacy of standard-of-care products plus remdesivir or hydroxycholoroquine or lopinavir/ritonavir (2114; NCT04330690). The adaptive, randomised, open-label, controlled clinical trial, in collaboration with countries around the world through the World Health Organization intends to enrol approximately 2900 patients in Canada [109] .
In August 2020, QuantumLeap Healthcare Collaborative initiated phase II I-SPY-COVID trial to evaluate efficacy of remdesivir in combination with cenicriviroc [see Adis Insight Drug profile800043325], icatibant [see Adis Insight Drug profile800001708], razuprotafib [see Adis Insight Drug profile800035272] and apremilast [see Adis Insight Drug profile800019919] in patients with acute respiratory distress syndrome associated with COVID-19 infections (NCT04488081). An open label, randomised trial intends to enrol 1500 patients in the US [110] . Company announced the enrollment of the first patient in the trial [111] .
In October 2020, BioSig Technologies and ViralClear Pharmaceuticals announced that it has stopped enrollments and halted the phase II trial that designed to evaluate the efficacy and safety of merimepodib [see Adis Insight Drug profile 800008158] in combination with remdesivir in patients with COVID-19 infections (VC02-01; NCT04410354). The double blind, randomised, placebo-controlled trial was initiated in June 2020 in USA. The recent results showed the trial would not meet its primary safety endpoints [112] . In September 2020, ViralClear Pharmaceuticals expanded the size of the trial from 40 to 80 hospitalised COVID-19 patients, and that limited enrollment to seriously ill patients, (NIAID Grade 3, who required high flow, high concentration oxygen to maintain adequate oxygenation). At the time review of the data by the SMC, 44 patients had been enrolled in the trial of whom 42 had received study drug (either merimepodib solution or matching placebo). The most recent review of the data documented all 22 Grade 4 patients were discharged from the hospital and did not relapse during the 37 day follow-up period. However, patients who were NIAID Grade 3 patients (n = 20) at the time of enrollment had markedly different outcomes. Specifically, the unblinded SMC detected an imbalance in survival rates in these NIAID Grade 3 patients between the placebo and merimepodib making it unlikely that the trial would meet its primary safety endpoints. The company has therefore elected to stop enrollment into the clinical trial. Patients will be followed as per the protocol for safety monitoring; however, no further study drug treatments will be administered. The first patient was dosed in June 2020 [113] [114] .
In March 2021, Gilead Sciences completed a phase I/II trial that evaluated the safety, efficacy, and pharmacokinetics of remdesivir administered by inhalation for early stage COVID-2019 infections (NCT04539262; GS-US-553-9020). The randomised study was initiated in September 2020, and enrolled 156 patients in the US [115] .
In March 2020, Gilead Sciences initiated an expanded access treatment protocol for remdesivir for the treatment of COVID-19 infections in the US, the UK, Belgium, Canada, France, Germany, Italy, Israel, Netherlands, Romania, Spain, Switzerland, Australia, Austria, Cyprus, Croatia, Denmark, Estonia, Greece, Hungary, Ireland, Iceland, Czech Republic, Poland, Portugal, Slovakia and Slovenia (GS-US540-5821; EudraCT2020-001453-49; NCT04323761). In April 2020, Froedtert & the Medical College of Wisconsin granted an approval for the enrollment in the expanded access programme [116] [117] [118] .
In November 2020, the US FDA announced that the SOLIDARITY trial did not find a statistically significant difference in mortality between the remdesivir arm and the standard-of-care arm [119] .
In February 2020, Gilead Sciences reported that remdesivir was purportedly used in treating the first case of 2019 novel coronavirus (2019-nCoV), in the US. There was no data for remdesivir displaying activity against 2019-nCoV, but data was available for other coronaviruses [120]
Prior to August 2023, Gilead Sciences completed the phase I trial that evaluated the pharmacokinetics of remdesivir and its metabolites in participants with normal hepatic function and moderate or severe hepatic impairment.(GS-US-540-9014). The trial enrolled 32 participants in the US [121]
Preclinical studies
In February 2022, pharmacodynamics data from a preclinical studies in COVID-2019 infections released by Gilead Sciences [122] .
In vitro testing conducted by Gilead has demonstrated that remdesivir is active against the virus that causes COVID-19 [85] .
Inhalation (nanopartical formulation)
In July 2020, NeuroActiva initiated the phase I NEUROSIVIR trial to evaluate the safety, tolerability and pharmacokinetics of inhaled nanoparticle formulation of remdesivir alone and in combination with traneurocin [see Adis Insight Drug Profile 800051889] in healthy adults (NCT04480333). The randomised, placebo controlled trial intends to enrol approximately 48 volunteers in the US [123] .
Compassionate use
In May 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency's (EMA) recommended expanding the compassionate use of remdesivir for the treatment of patients with COVID-2019 infections. The compassionate use recommendations covered the treatment of hospitalised patients requiring supplemental oxygen, non-invasive ventilation, high-flow oxygen devices or ECMO (extracorporeal membrane oxygenation) [124] .
In April 2020, EMA’s human medicines committee (CHMP) gave recommendations for the compassionate use programmes of remdesivir for treatment of coronavirus infections (COVID-19) in the European Union. earlier, Estonia, Greece, the Netherlands and Romania requested an opinion from the CHMP on the conditions for early access to remdesivir through compassionate use could be given to patients with COVID‑19 [125] .
Remdesivir is available through an expanded access programme conducted by U.S. Army Medical Research and Development Command for the treatment of COVID-2019 infections in the US (S-20-01; NCT04302766) [126] .
Gilead Sciences provided remdesivir for compassionate use to 2 patients, one a female patient in the Royal Free Hospital in London in October and one in Guinea the following month [127] .
Gilead Sciences is also providing remdesivir for compassionate use to patients with COVID-2019 infections for emergency treatment outside of ongoing clinical studies [89] .
In July 2020, Gilead Sciences released efficacy and safety data of remdesivir from compassionate use programme for COVID-2019 infections in pediatric patients and in pregnant and postpartum women [83] . In April 2020, Gilead Sciences released efficacy and safety data of remdesivir from compassionate use programme for COVID-2019 infections [128] [129] . Gilead Sciences in April 2020, reported that intravenous infusion of remdesivir demonstrated clinical improvement in first 53 patients who received treatment in compassionate programme [79] .
Ebola virus infections
In August 2019, based on independent Data and Safety Monitoring Board’s (DSMB) recommendation, Gilead Sciences, Ridgeback Biotherapeutics and National Institute of Allergy and Infectious Diseases prematurely prematurely terminated the phase II/III PALM trial designed to assess the safety and effectiveness of mAb 114; REGN 3470/3471/3479 , porgaviximab and remdesivir separately in patients with Ebola virus infections (19-I-0003; NCT03719586). The open-label, randomised, controlled study was initiated in October 2018, and enrolled 1 044 patients in the US and Congo [130] [131] .
In October 2019, National Institute of Allergy and Infectious Diseases completed the phase II PREVAIL IV trial to assess the antiviral activity, safety and tolerability of remdesivir 100mg IV in male Ebola survivors with evidence of Ebola virus persistence (999916137; 16-I-N137; NCT02818582). The randomised 1:1, double-blind, parallel, placebo-controlled, two-phase (treatment and longer-term follow-up) trial was initiated in June 2016 and enrol approximately 30 patients in the Guinea and Liberia. Longer-term clearance of Ebola virus will be assessed during the 5-month follow-up phase [132] .
In July 2021, Gilead sciences initiated a phase I trial to evaluate the pharmacokinetics of remdesivir and metabolites in participants with normal renal function and renal impairment (ACTRN12620001048976; 380566). The open label trial intends to enroll 80 participants in Germany, New Zealand, Puerto Rico and the US [133] . In September 2022, results from the trial were presented at the 2022 American College of Clinical Pharmacology Annual Meeting (ACCP-2022) [134] .
Gilead initiated a phase I trial in healthy volunteers to evaluate the safety, tolerability and pharmacokinetics of remdesivir [135] .
Preclinical studies
In a monkey model of Ebola virus infections, remdesivir displayed efficacy as well as potential for broad-spectrum anti-filovirus activity with 100% survival of monkeys [136] .
Remdesivir has a broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple viral pathogens, including Ebola, Marburg, MERS, SARS and SARS-CoV-2 [85] [9] .
Supply arrangement
In July 2020, Gilead Sciences entered into an agreement with U.S. Department of Health and Human Services (HHS) to manage the allocation of remdesivir to hospitals until the end of September [137] .
In October 2020, Gilead Sciences signed a joint procurement agreement (JPA) that will enable rapid and equitable access to remdesivir (Veklury®) for the treatment of COVID-19 in the European Union (EU). The JPA enables participating countries in the EU and the European Economic Area (EEA) and the United Kingdom to purchase remdesivir for both real-time demand and stockpiling needs, coordinated by the European Commission. The agreement covers purchases of remdesivir over the next six months and has the option to be extended [138] .
In July 2020, Gilead entered into an agreement with the European Commission to enable the European Commission to secure treatment doses of remdesivir (Veklury) in order to meet immediate needs. The drug will be made available in the member states and the UK from early August [139] .
Financial information
In July 2020, The emergency authorization of remdesivir received $US6.5 billion in NIH funding for the treatment of COVID-19 infection [140] .
Patent Information
As at December 2020, Gilead Sciences was issued patent protection for remdesivir in the US and in the European Union valid through 2035 [141]
Drug Properties & Chemical Synopsis
- Route of administration Inhalation, IV
- Formulation Infusion, Injection, unspecified
- Class Adenine nucleotides, Amines, Antivirals, Esters, Furans, Nitriles, Phosphorus compounds, Pyridazines, Pyrroles, Small molecules, Triazines
- Target RNA replicase
- Mechanism of Action RNA replicase inhibitors
-
WHO ATC code
J05A-B16 (Remdesivir)
-
EPhMRA code
J5 (Antivirals for Systemic Use)
N7 (Other CNS Drugs)
R7X (All Other Respiratory System Products)
- Chemical name 2-ethylbutyl ((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[1,2-b]pyridazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate
- Molecular formula C28 H36 N5 O8 P
- SMILES C(C(NP(=O)(OC1C=CC=CC=1)OCC1OC(C(C1O)O)(C#N)C1=CC=C2C(=CC=NN21)N)C)(=O)OCC(CC)CC
-
Chemical Structure
- CAS Registry Number 1809249-37-3
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
adult respiratory distress syndrome |
Arm Group Description |
Monocyte differentiation antigen CD14 histamine receptor H2 |
|
|
cOVID 2019 infections |
Arm Group Description |
Monocyte differentiation antigen CD14 histamine receptor H2 |
|
|
cOVID 2019 infections |
Eligibility Criteria |
protein tyrosine phosphatase, receptor type F L-Aspartic acid ALT |
|
|
cOVID 2019 infections |
Outcome Measure |
Tumor necrosis factor alpha (TNF-alpha) KLHL2 Interleukin-6 (IL-6) C-reactive protein (CRP) |
|
|
cOVID 2019infections |
Outcome Measure |
D-dimer |
|
|
COVID-19 pneumonia |
Outcome Measure |
L-Aspartic acid ATP-binding cassette, sub-family B (MDR/TAP), member 7 Alkaline phosphatase (ALPL) |
|
|
COVID-19 respiratory infection |
Arm Group Description |
Monocyte differentiation antigen CD14 histamine receptor H2 |
|
|
COVID-19 respiratory infection |
Arm Group Label |
interferon, beta 1, fibroblast |
|
|
COVID-19 respiratory infection |
Brief Title |
interferon, beta 1, fibroblast |
|
|
COVID-19 respiratory infection |
Outcome Measure |
Fibrinogen Ferritin D-dimer C-reactive protein (CRP) |
|
|
respiratory insufficiency |
Outcome Measure |
Lactate dehydrogenase (LDH) Fibrinogen Ferritin D-dimer C-reactive protein (CRP) |
|
|
respiratory tract infections |
Outcome Measure |
Tumor necrosis factor alpha (TNF-alpha) Interleukin-6 (IL-6) C-reactive protein (CRP) |
|
|
SARS-CoV-2 acute respiratory disease |
Eligibility Criteria |
protein tyrosine phosphatase, receptor type F L-Aspartic acid ALT |
|
|
SARS-CoV-2 acute respiratory disease |
Outcome Measure |
Lactate dehydrogenase (LDH) Fibrinogen Ferritin D-dimer C-reactive protein (CRP) |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Remdesivir - Gilead Sciences | 1-Methylnicotinamide | Outcome Measure |
| ACE2 | Outcome Measure | |
| Aldosterone | Outcome Measure | |
| Alkaline phosphatase (ALPL) | Outcome Measure | |
| ALT | Eligibility Criteria | |
| Angiotensin II | Outcome Measure | |
| ATP-binding cassette, sub-family B (MDR/TAP), member 7 | Outcome Measure | |
| B-lymphocyte antigen CD19 | Outcome Measure | |
| Bilirubin | Detailed Description, Outcome Measure | |
| BNP | Detailed Description, Outcome Measure | |
| C-reactive protein (CRP) | Detailed Description, Eligibility Criteria, Outcome Measure | |
| Canrenone | Arm Group Description, Brief Title, Official Title | |
| Cardiac Troponin I | Detailed Description, Eligibility Criteria, Outcome Measure | |
| Cardiac Troponin T | Outcome Measure | |
| CD3 gamma chain (CD3G) | Outcome Measure | |
| CD56 | Outcome Measure | |
| Creatine | Eligibility Criteria, Outcome Measure | |
| Creatinine | Detailed Description, Outcome Measure | |
| Cystatin C | Outcome Measure | |
| D-dimer | Detailed Description, Eligibility Criteria, Outcome Measure | |
| dermo-distortive urticaria | Eligibility Criteria | |
| Escitalopram | Arm Group Label | |
| Factor V | Eligibility Criteria | |
| Fc fragment of IgG, low affinity IIIb, receptor (CD16b) | Outcome Measure | |
| Fc gamma RIIIa | Outcome Measure | |
| Ferritin | Detailed Description, Eligibility Criteria, Outcome Measure | |
| Fibrinogen | Detailed Description, Eligibility Criteria, Outcome Measure | |
| gamma-glutamyltransferase 2 | Outcome Measure | |
| gamma-glutamyltransferase light chain 3 | Outcome Measure | |
| GGT | Outcome Measure | |
| GGTLC4P | Outcome Measure | |
| GGTLC5P | Outcome Measure | |
| Granulocyte-macrophage colony-stimulating factor (GM-CSF) | Outcome Measure | |
| histamine receptor H2 | Arm Group Description | |
| HLA-DR | Outcome Measure | |
| IFN-alpha 2 | Arm Group Description | |
| interferon, beta 1, fibroblast | Arm Group Label, Brief Title | |
| Interleukin 1 alpha (IL-1α) | Outcome Measure | |
| Interleukin 1 Beta (IL-1β) | Outcome Measure | |
| interleukin 6 receptor | Brief Summary, Official Title, Outcome Measure | |
| Interleukin-10 (IL-10) | Outcome Measure | |
| Interleukin-6 (IL-6) | Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure | |
| Interleukin-8 (IL-8) | Outcome Measure | |
| KIM-1 | Outcome Measure | |
| KLHL2 | Outcome Measure | |
| L-Aspartic acid | Eligibility Criteria, Outcome Measure | |
| L-FABP | Outcome Measure | |
| Lactate dehydrogenase (LDH) | Outcome Measure | |
| Monocyte differentiation antigen CD14 | Arm Group Description, Arm Group Label, Brief Title, Official Title | |
| N-Acetyl-L-aspartic acid | Eligibility Criteria | |
| NGAL | Outcome Measure | |
| Nicotinic acid adenine dinucleotide | Outcome Measure | |
| NLR family, pyrin domain containing 3 | Arm Group Description | |
| Oxytocin | Arm Group Label, Brief Title, Official Title | |
| PAI-1 | Outcome Measure | |
| PDZ and LIM domain 7 | Eligibility Criteria | |
| phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha | Outcome Measure | |
| protein tyrosine phosphatase, receptor type F | Eligibility Criteria | |
| Prothrombin (PT) | Eligibility Criteria, Outcome Measure | |
| Renin | Arm Group Description, Brief Summary, Outcome Measure | |
| seryl-tRNA synthetase | Arm Group Description, Arm Group Label | |
| SH3 and cysteine rich domain 3 | Outcome Measure | |
| T-Cell differentiation antigen CD8 | Eligibility Criteria, Outcome Measure | |
| T-cell receptor CD3-epsilon (CD3e) | Outcome Measure | |
| T-cell receptor T3 delta chain (CD3d) | Outcome Measure | |
| T-cell surface antigen CD4 | Eligibility Criteria, Outcome Measure | |
| Thyroid stimulating hormone beta (TSH) | Outcome Measure | |
| Triiodothyronine | Outcome Measure | |
| Tubulin beta class IVb | Outcome Measure | |
| Tumor necrosis factor alpha (TNF-alpha) | Outcome Measure |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| COVID 2019 infections | in patients aged 12 years and older | In adolescents, In adults | Marketed | USA | IV / Infusion | Gilead Sciences | 23 Oct 2020 |
| COVID 2019 infections | - | Adjuvant therapy, Monotherapy | Marketed | Egypt | IV / Infusion | Gilead Sciences | 04 Feb 2021 |
| COVID 2019 infections | in combination with lopinavir/ritonavir | Adjuvant therapy, Combination therapy | Marketed | Egypt | IV / Infusion | Gilead Sciences | 04 Feb 2021 |
| COVID 2019 infections | Adjunctive to standard-of-care Adjunctive to standard-of-care; with conditional approval | Adjunctive treatment | Registered | Japan, Singapore, Taiwan | IV / Infusion | Gilead Sciences | 10 Jun 2020 |
| COVID 2019 infections | - | - | Registered | United Arab Emirates | IV / Infusion | Gilead Sciences | 03 Jul 2020 |
| COVID 2019 infections | restricted emergency use | In adolescents, In adults, In children | Registered | India | IV / Infusion | Dr Reddys Laboratories, Gilead Sciences | 01 Jun 2020 |
| COVID 2019 infections | age 12 years and older (and weighing at least 40 kg), provisional approval | In adolescents, In adults, In the elderly | Registered | Australia | IV / Infusion | Gilead Sciences | 10 Jul 2020 |
| COVID 2019 infections | emergency use authorisation in patients aged less than 12 years | In children | Registered | USA | IV / Infusion | Gilead Sciences | 23 Oct 2020 |
| COVID 2019 infections | in patients from 12 years of age with pneumonia who require supplemental oxygen | In adolescents, In adults, In children | Registered | European Union, Iceland, Liechtenstein, Norway | IV / Infusion | Gilead Sciences | 06 Jul 2020 |
| COVID 2019 infections | adults and paediatric patients (at least 4 weeks of age and weighing at least 3 kg), provisional approval. | In adolescents, In adults, In infants, In neonates, In the elderly | Registered | Australia | IV / Infusion | Gilead Sciences | 06 May 2022 |
| COVID 2019 infections | - | In children, In infants, In neonates | Preregistration | European Union | IV / Infusion | Gilead Sciences | 16 Sep 2022 |
| COVID 2019 infections | Adjunctive to standard-of-care | Adjunctive treatment | Phase III | France, Germany, Hong Kong, Italy, Netherlands, South Korea, Spain, Sweden, Switzerland, USA, United Kingdom | IV / Infusion | Gilead Sciences | 29 Apr 2020 |
| COVID 2019 infections | Adjunctive to standard-of-care Adjunctive to SOC | Adjunctive treatment | Phase III | Austria, Belgium, Hungary, Ireland, Luxembourg, Norway, Portugal | IV / Infusion | Gilead Sciences, INSERM | 22 Mar 2020 |
| COVID 2019 infections | Adjunctive to standard-of-care | Adjunctive treatment | Phase III | China | IV / Infusion | China-Japan Friendship Hospital, Gilead Sciences | 01 Mar 2020 |
| COVID 2019 infections | - | Early-stage disease, In adolescents, In adults, In children, In the elderly | Phase III | Denmark, Portugal, Spain, USA, United Kingdom | IV / Infusion | Gilead Sciences | 22 Sep 2020 |
| COVID 2019 infections | - | In adolescents, In adults, In the elderly | Phase III | Portugal, USA | IV / Infusion | Gilead Sciences | 09 Mar 2021 |
| COVID 2019 infections | - | - | Phase III | China | IV / Injection | Capital Medical University, Gilead Sciences, Chinese Academy of Medical Sciences, China-Japan Friendship Hospital | 12 Feb 2020 |
| COVID 2019 infections | in combination with baricitinb In combination with baricitinib | Combination therapy | Phase III | Japan, Mexico, Singapore, South Korea, USA | IV / Infusion | National Institute of Allergy and Infectious Diseases | 08 May 2020 |
| COVID 2019 infections | - | - | Phase III | Japan, Mexico, Singapore, South Korea | IV / Infusion | Gilead Sciences, National Institute of Allergy and Infectious Diseases | 21 Feb 2020 |
| COVID 2019 infections | - | In adolescents, In children, In infants, In neonates | Phase II/III | USA | IV / Infusion | Gilead Sciences | 23 Jul 2020 |
| COVID 2019 infections | - | In adolescents, In adults, In children, In infants, In neonates | Phase II/III | Italy, Spain, United Kingdom | IV / Infusion | Gilead Sciences | 23 Jul 2020 |
| COVID 2019 infections | in combination with optimised supportive care | Adjunctive treatment | Phase II | Canada | IV / Infusion | Gilead Sciences | 18 Mar 2020 |
| COVID 2019 infections | - | Early-stage disease | Phase I/II | USA | Inhalation / unspecified | Gilead Sciences | 14 Sep 2020 |
| COVID 2019 infections | - | - | Phase I | New Zealand, Puerto Rico | IV / Infusion | Gilead Sciences | 26 Jul 2021 |
| COVID 2019 infections | in combination with traneurocin | Combination therapy, In volunteers | No development reported (I) | USA | Inhalation / unspecified | NeuroActiva | 28 Aug 2023 |
| COVID 2019 infections | - | - | No development reported (Clinical) | Israel | IV / Infusion | Gilead Sciences | 28 Apr 2023 |
| COVID-19 pneumonia | in combination with tocilizumab associated with COVID-2019 infections | Combination therapy | Phase III | Brazil, Canada, Russia, Spain, USA | IV / Infusion | Gilead Sciences, Roche | 16 Jun 2020 |
| Ebola virus infections | - | - | Phase II | Congo, Guinea, Liberia, USA | IV / Infusion | Gilead Sciences, National Institute of Allergy and Infectious Diseases | 25 Oct 2018 |
| Neurological disorders | in combination with traneurocin | In volunteers, Monotherapy | No development reported (I) | USA | Inhalation / unspecified | NeuroActiva | 28 Aug 2023 |
| Neurological disorders | in combination with traneurocin | Combination therapy, In volunteers | No development reported (I) | USA | Inhalation / unspecified | NeuroActiva | 28 Aug 2023 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Gilead Sciences | Originator | USA |
| Gilead Sciences | Owner | USA |
| Viatris Inc | Market Licensee | World |
| Jubilant Life Sciences | Market Licensee | India |
| Zydus Cadila | Market Licensee | India |
| Cipla | Market Licensee | India, South Africa |
| Dr Reddys Laboratories | Market Licensee | India |
| Hetero Drugs | Market Licensee | India |
| Ligand Pharmaceuticals | Technology Provider | USA |
| Quantum Leap Healthcare Collaborative | Collaborator | USA |
| Cardiothoracic Surgical Trials Network | Collaborator | USA |
| National Heart, Lung and Blood Institute | Collaborator | USA |
| Medical College of Wisconsin | Collaborator | USA |
| Capital Medical University | Collaborator | China |
| Roche | Collaborator | Switzerland |
| INSERM | Collaborator | France |
| Intermountain Healthcare | Collaborator | USA |
| Center for Disease Control | Collaborator | |
| Daewoong Pharmaceutical | Collaborator | South-Korea |
| NeuroActiva | Collaborator | USA |
| National Institute of Allergy and Infectious Diseases | Collaborator | USA |
| United States Army Medical Research Institute of Infectious Diseases | Collaborator | USA |
| University of Copenhagen | Collaborator | Denmark |
| NRx Pharmaceuticals | Collaborator | USA |
| Chinese Academy of Medical Sciences | Collaborator | China |
| Kirby Institute for infection and immunity in society | Collaborator | Australia |
| China-Japan Friendship Hospital | Collaborator | China |
| Medical Research Council | Collaborator | England |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| Redyx | Dr Reddys Laboratories | COVID 2019 infections | India |
| VEKLURY | Gilead Sciences | COVID 2019 infections | Australia |
| Veklury | Gilead Sciences | COVID 2019 infections | European Union, Japan, Singapore, USA |
Scientific Summary
Pharmacokinetics
In the phase III REDPINE trial of remdesivir, observed PK associated with increased metabolite levels in patients with severely impaired kidney function, no dose adjustment is recommended for remdesivir in COVID-19 patients with eGFR < 30 mL/min/1.73 m2, regardless of the need for dialysis. geometric mean exposures (AUCtau) increased up to 553% for the GS-441524 metabolite (dependent on renal elimination) and to a lesser degree GS-704277 (294%, minor renal elimination) and remdesivir (78.9%; an increase explained by factors other than renal function, namely, hospitalization and body weight). The increased PK exposures were not associated with new safety signals in this study (n=163 remdesivir, n=80 placebo) [61] [60] .
Results from a phase II/III CARAVAN trial demonstrated that, the final PopPK model was a two-compartment model for RDV and GS-704277, three-compartment model for GS-441524 with first order elimination. Fixed allometry with 0.75 coefficient on clearance (CL) and 1.0 for volume of distribution (Vc) was incorporated to account for significant effect of body weight (BW) on RDV and metabolites. An a priori maturation function was also added. No additional covariates were identified for RDV; ferritin, and baseline bilirubin, potential indicators of COVID-19 disease severity, had the largest impact on GS-704277 (-24% to +67%, relative to median) and GS-441524 (- 24% to 64%) exposures within the pediatric population, respectively. Based on the final PopPK model, simulated mean pediatric exposures (AUCtau, Cmax and Ctau) were modestly increased (RDV, 33% to 129%; GS-704277, 37% to 124%; GS-441524, 0% to 60%) but the range of exposures was largely overlapping, when compared to adult phase III COVID-19 population. No trends were identified between PK exposures and safety (7 most common AEs) except for GS-441524 increase in those with vs without AE of acute kidney injury. No trends were identified between PK exposures and efficacy end points evaluated in this study [106] [101] .
In a phase I trial evaluating the pharmacokinetics of remdesivir and metabolites in patients with normal renal function and renal impairment, plasma pharmacokinetics of remdesivir and peripheral blood mononuclear cell (PBMC) levels of active metabolite GS-443902 were not affected by mild, moderate, or severe renal impairment. Up to 2-fold increase in GS-704277 and GS-441524 metabolite levels were observed in mild and moderate renal impairment, and approximately 4-fold increase of GS-441524 metabolite was observed in severe renal impairment [134] [133] .
Adverse Events
In a compassionate use programme in pediatric patients and in pregnant and postpartum women, treatment with remdesivir was well tolerated and no new safety signals were reported. The most common AEs were observed to be due to underlying disease and most laboratory abnormalities were reported to be grade 1–2 [129] [83]
Treatment with remdesivir in a phase III SIMPLE-severe trial for COVID-2019 infections showed that the drug was generally well-tolerated in both the 5-day and 10-day treatment groups. The most common adverse events (AE) occurring in more than 10% of patients in either group were nausea (5-day: 10.0%, n=20/200 vs. 10-day: 8.6%, n=17/197) and acute respiratory failure (5-day: 6.0%, n=12/200 vs. 10-day: 10.7%, n= 21/197). Grade 3 or higher liver enzyme (ALT) elevations occurred in 7.3% in 10 days group and 2% in 5 days group, with 3% of patients discontinuing remdesivir treatment due to elevated liver tests. Also, AST increase in 5 days vs 10 days group was 3% vs 6% respectively. Study drug-related serious adverse event were observed in 2% patients in both groups. AE leading to discontinuation were observed in 5% and 10% patients in 5 day and 10 day groups respectively [26] [85] [87] .
In the phase III SIMPLE trial (SIMPLE moderate), conducted in patients with moderate manifestations of COVID-19, remdesivir in combination with standard of care was generally well-tolerated in both the 5-day and 10-day treatment groups and did not showed any new safety signal. Adverse events were reported in 51% (97/191) patients in 5-day course, in 55% (106/193) patients in 10-day course and 45% (90/200) patients in standard-of-care group. Grade >3 AE were reported in 10% (20/191) patients in 5-day course, in 11% (21/193) patients in 10-day course and 12% (24/200) patients in standard-of-care group. Serious events were reported in 4% (8/191) patients in 5-day course, in 4% (7/193) patients in 10-day course and 9% (18/200) patients in standard-of-care group. The most common adverse events occurring in more than 5 percent of patients in both treatment groups were nausea (5-day: 10% / 10-day: 9% / SOC: 3%), diarrhoea (5-day: 5% / 10-day: 5% / SOC: 7%) and headache (5-day: 5% / 10-day: 5% / SOC: 3%) [84] [90] .
In the phase III ACTT-1 trial, treatment with remdesivir was found to be generally safe and well tolerated. Overall, the incidence of adverse events associated with remdesivir was similar to placebo, with no new safety signals identified. Rates of serious adverse events (SAEs) were numerically higher in the placebo group compared with the remdesivir group (PBO + SOC: 32%; Veklury + SOC: 25%). Treatment discontinuation, all cause grade 3 and 4 adverse events and laboratory abnormalities were similar across groups [91] [93] .
Results from the phase III CAP-China remdesivir 1 trial demonstrated that remdesivir was well tolerated with grade 3 and grade 4 adverse events compared to fewer serious adverse events in 5 day and 10 day arm. Most common adverse events include nausea, headache and hypokalemia. Incidence of adverse events leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. No statistically significant change was observed in renal and liver function tests between the remdesivir 5 day and 10 day groups compared to the standard of care only group at day 14 [99] . The further analysis of remdesivir effect on renal function in patients with COVID-19 infections demonstrated that patients treated with remdesivir (n=822) reported less frequent acute kidney injury events, compared with the patients receiving standard of care treatment (n=183) (7% vs 10%, p=0.03). After adjustment for age, remdesivir was not significantly associated with the risk of acute kidney injury compared to standard of care (RR=0.66; 95% CI 0.40, 1.09). Patients with baseline estimated glomerular filtration rate (eGFR) >90 ml/min reported more acute kidney injury events, with few events occurring in patients with a baseline eGFR 50-59 ml/min. At day 14, in patients with stage 3 acute kidney injury, creatinine values returned to baseline after treatment with remdesivir (n=2, 0.2%), while it remained elevated in patients receiving standard of care treatment (n=4, 2%). No difference in acute kidney injury was observed between treatment arms in patients with a history of chronic kidney disease (remdesivir: n=6 [12%] vs standard of care: n=2 [40%]; p=0.14). The open-label trial evaluated 1005 patients with similar creatinine and eGFR values in both the treatment arms, collected through day 14 [100] [97]
In the phase III REDPINE trial of remdesivir, absence of any new safety signals was observed [61] [60] .
Updated results from the phase II/III CARVAN trial, treatment with remdesivir was generally well tolerated among pediatric patients hospitalized with COVID-19.Overall, 38 patients (72%) experienced AEs, with 11 patients (21%) experiencing serious adverse events (SAEs) that were determined not to be study-drug related including 3 participant deaths which were consistent with the patients underlying medical condition prior to study entry or with COVID-19 disease during hospitalization [105] . In the analysis, the most common adverse event in patients taking remdesivir was constipation (17%), followed by acute kidney injury (11%), hyperglycemia (9%) and pyrexia (9%). Grade 3 lab abnormalities were reported in 42%; most common being decreased haemoglobin (n=9) and decreased eGFR levels (n=7). No safety trends related to RDV were apparent [104] [103] . Results from phase II/III CARAVAN trial of remdesivir (RDV) in hospitalized pediatric patients with PCR-confirmed COVID-19 showed that, most RDV discontinuations were due to clinical improvement. Most (78%) had =1 AE, including 17% with study drug-related AEs; 7% discontinued study drug due to an AE. Serious AEs were reported for 33% of patients; no SAEs were study drug related. Two patients died within 30 days of completing treatment. Grade 3 or 4 lab abnormalities were reported in 52%; those reported in =1 patient were decreased hemoglobin (n=5), and hypoglycemia, glycosuria, and increased PTT (n=2 each). No safety trends related to RDV were apparent [101] [102] .
Adverse events data obtained from phase III data indicated similarity in safety profile of the treatment and placebo groups. the most common treatment emergent adverse event was reported to be nausea and headache in the treatment group (=5%). No new safety signals were identified. One death was reported at day 59 in the placebo group [72] [143] .
New results of the phase III PINETREE trial showed that a 3-day course of intravenously administered remedesivir was safe, well tolerated and highly effective at preventing COVID-19 related hospitalization or death in high-risk non-hospitalized COVID-19 patients. The most common comorbidities were diabetes mellitus (62%), obesity (56%; median BMI, 30.7), and hypertension (48%) (n=562). No deaths occurred in either arm by day 28. There was no difference between arms in time-weighted average change in nasopharyngeal viral loads from baseline up to day 7. The proportion of patients with AEs was similar between arms. The most common AEs in the RDV arm were nausea (11%), headache (6%), and diarrhea (4%) [69] . Data from the phase III PINETREE trial showed that, remedesivir found to be safe and well tolerated. Adverse events had occurred in 118 of 279 patients (42.3%) in the remdesivir group and in 131 of 283 (46.3%) in the placebo group. The most common non-serious adverse events that occurred in at least 5% of patients in both groups were nausea, headache, and cough. Adverse events that were determined by the investigators to be related to the trial regimen occurred in 34 of 279 patients (12.2%) in the remdesivir group and in 25 of 283 (8.8%) in the placebo group. Fewer patients in the remdesivir group than in the placebo group had serious adverse events (5 of 279 patients [1.8%] vs. 19 of 283 patients [6.7%]). By day 28, laboratory abnormalities of grade 3 or higher had occurred in 29 of 279 patients (10.4%) in the remdesivir group and in 23 of 283 (8.1%) in the placebo group. At day 14, the mean (±SD) change from baseline in creatinine clearance was minimal (0.26±21.2 ml per minute in the remdesivir group and 1.9±18.6 ml per minute in the placebo group). Similarly, at day 14, the mean change from baseline in alanine aminotransferase levels was minimal (−3.0±21.6 U per liter in the remdesivir group and −1.0±27.4 U per liter in the placebo group [70] [71] [73] .
In a phase I trial evaluating the pharmacokinetics of remdesivir and metabolites in patients with normal renal function and renal impairment, remdesivir treatment was generally well tolerated, and no treatment emergent grade 3 or 4 adverse events were reported in any group [134] [133] .
Pooled analysis
The results of phase III ACTT-1 trial, phase III PINETREE trial, phase III REDPINE trial in COVID 19 infections demonstrated the hepatic safety of remdesivir (RDV). Hepatic AEs were reported at similar rates for each treatment group in ACTT-1 (RDV: 71 [13%]; placebo: 80 [16%]) and PINETREE (RDV: 1 [0.4%]; placebo: 4 [1.4%]). In REDPINE, 12 (7.4%) and 2 (2.5%) participants in the RDV and placebo groups. Most of the adverse events were increased levels of ALT/AST-related terms. In all 3 studies, laboratory abnormalities of increased levels of ALT, AST, and bilirubin of any grade were each reported in similar or lower percentages with RDV compared with placebo [59] .
Pharmacodynamics
Summary
Results from in vitro studies demonstrated the consistent and durable antiviral activity of remdesivir (Veklury®) against ten SARS-CoV-2 variants, including Omicron. The study results showed similar activity of Veklury against the variants and an early ancestral A lineage isolate detected in Seattle, WA (WA1 strain). Specifically, Delta and Omicron variants both remained fully susceptible to Veklury, and these laboratory results demonstrated that Veklury has remained active against all major variants isolated over the past two years. Veklury directly inhibited viral replication inside host cells by targeting the SARS-CoV-2 RNA-dependent RNA polymerase. On entering the body, Veklury transformed into the active triphosphate metabolite, which is then incorporated into the viral RNA and stops replication of the virus within the infected cells. The study analyzed nearly 6 million publicly available variant isolate sequences and confirmed that the nsp12 protein, the RNA polymerase target of Veklury, is highly conserved across all variants. Further characterization confirmed that none of the few identified nsp12 mutations prevalent in some of the SARS-CoV-2 variants affected the virus susceptibility to Veklury [122] .
Remdesivir was shown in vitro to inhibit Ebola virus (Kikwit and Makona variants), Sudan and Marburg virus at EC50 = 0.01 to 0.20µM. In Ebola virus(EV)-infected rhesus monkeys, intramuscular injection of remdesivir led to 50% survival versus 0% survival in placebo-treated animals (p<0.003). Intravenous injection of remdesivir resulted in 100% survival in EV-infected animals, with a mean plasma viral RNA reduction of 5log10 copies/mL relative to placebo (p<0.001), as well as suppression of EV infection signs [136] . In rhesus monkey filovirus infection models, remdesivir significantly reduced systemic viraemia and ameliorated severe clinical disease signs and anatomic pathology. In mice infected with MERS-CoV, twice daily SC administration of remdesivir, at dose 25 mg/kg, significantly reduced lung viral load and improved respiratory function. In rhesus monkeys, once-daily IV administration of remdesivir, at dose 5 mg/kg, initiated one day prior to MERS-CoV infection reduced lung viral load, improved clinical disease signs, and ameliorated severe lung pathology [142] .
Therapeutic Trials
Efficacy data obtained from a phase III trial indicated 87% of significant reduction compared to placebo (5.3% [15/283]) p=0.008, in risk for the composite primary endpoint of COVID-19 related hospitalisation or all cause death by day 28 (0.7% [2/279]). By Day 28, 81% reduction was reported in all-cause death or risk for the composite secondary endpoint of medical visits in participants treated with Veklury (1.6% [4/246]) compared with placebo (8.3% [21/252]) p=0.002. In either of the arms, no deaths were observed by day 28 [72] [73] .
Phase III
Updated efficacy data from phase III REDPINE study of remdesivir in patients with COVID-2019 infections showed that emergent amino acid substitutions in Nsp12 were observed in 8/41 (19.5%) in the remdesivir (RDV) group and 1/19 (5.3%) in the placebo group among 60 patients. The proportions of participants with all-cause death or IMV through Day 29 were comparable between participants in the RDV group with emergent Nsp12 substitutions (5/8, 62.5%) or without emergent Nsp12 substitutions (30/33, 90.9%). In 4 participants in the RDV group, Nsp12 substitutions with low-level reduced susceptibility to RDV were identified in samples collected 9 days after cessation of RDV treatment (2.9- to 3.4-fold change in EC50): M794I (n = 2), C799F (n = 1), and E136V (n = 1). Three of these 4 participants had received solid organ transplants and were receiving concomitant immunosuppressive therapies during the study [62] [60]
In a compassionate use programme treatment with remdesivir, 77 pediatric patients treated with remdesivir demonstrated significant improvement in clinical status by day 28, with 73 percent discharged from the hospital, 12 percent remained hospitalized but on ambient air and four percent had died. Of the 39 pediatric patients who required invasive mechanical ventilation at baseline, 80% patients of these critically ill patients were observed to recover whereas out of 38 patients not requiring invasive ventilation, 87% were observed to recover. Treatment of 86 pregnant and postpartum women with remdesivir showed that 96% of pregnant and 89% of postpartum women achieved improvement in oxygen support levels. Pregnant and postpartum women who had more severe illness at baseline were reported to achieve similar high rates of clinical recovery, at 93% and 89% respectively. Pregnant women not on invasive oxygen support at baseline were reported to have shortest median time to recovery (5 days), and both pregnant and postpartum women on invasive ventilation at baseline were reported to have similar median times to recovery (13 days). Earlier results from the compassionate use programme demonstrated improvement in oxygen support class in 68% of patients (n=36/53), with COVID-2019 infections over a median follow-up of 18 days from the first dose. More than half of patients on mechanical ventilation were extubated (57 percent, n=17/30) and nearly half of all patients (47 percent, n=25/53) were discharged from the hospital. After 28 days of follow-up, the cumulative incidence of clinical improvement, was reported to be 84% according to Kaplan-Meier analysis. Clinical improvement was reported to less frequent among patients on invasive ventilation versus noninvasive ventilation (HR: 0.33 [95% CI 0.16, 0.68]) and among patients at least 70 years of age (HR vs < 50 years: 0.29 [95% CI 0.11, 0.74]). The overall mortality rate was reported to be 13%. The mortality rate was higher in the subgroup of patients on invasive ventilation (18%), compared with patients on noninvasive oxygen support (5%). Mild to moderate liver enzyme elevations were reported in 23% of patients [128] [129] [83]
Updated results from the phase III SIMPLE-severe trial for COVID-19 infections showed that clinical outcomes varied by geography. Increased mortality and lower rate of clinical improvement, were observed in patients from Italy compared with other regions. At day 14, the overall mortality rate was 7% and 18% for all other countries and Italy, respectively. Clinical improvement at day 14, measured as ≥2-point increase in the ordinal scale, was lower in Italian patients (39%) versus all other countries combined (64%). The overall results showed that 5day remdesivir treatment was as effective as 10days. In a multivariable model, 5/10d remdesivir was significantly positively associated with clinical improvement (adjusted odds ratio [OR] 1.69, 95% CI: 1.08, 2.65; p = 0.0226). Age < 65y (p < 0.0001) and region of treatment (Europe and NA vs Asia, p< 0.0001 each were the significant covariables positively associated with clinical improvement. Other factors that were not significantly associated with clinical improvement, included gender, race, ethnicity, baseline oxygen support, duration of symptoms and hospitalization, obesity, and baseline transaminase levels. Earlier data showed significant improvement in clinical recovery and a 62 percent reduction was observed in the risk of mortality in comparison to standard of care. Recovery was observed in 74.4% remdesivir treated patients on day 14 in comparison to 59% patients receiving standard of care. The mortality rate for patients treated with remdesivir in the analysis was observed to be 7.6% at day 14 in comparison to 12.5% patients not taking remdesivir (adjusted odds ratio 0.38, 95% confidence interval 0.22-0.68, p=0.001). Median follow-up of 14 days, the rates and likelihood of recovery were observed to be lower in patients who received concomitant hydroxychloroquine in comparison to patients treated with remdesivir who did not receive hydroxychloroquine (57 percent vs. 69 percent, covariate-adjusted HR [95% CI] 0.61 [0.45, 0.83], p=0.002). In an exploratory analysis, patients in the study who received remdesivir within 10 days of symptom onset had improved outcomes compared with those treated after more than 10 days of symptoms. Five and 10 day treatment course showed similar outcomes (odds ratio 0.75; 95% CI, 0.51 to 1.12) [26] . Pooling data across treatment arms, by day 14, 62% patients treated early were able to be discharged from the hospital, compared with 49% patients who were treated late [81] [82] [83] [85] [87] .
Final results from the phase III ACTT-1 trial showed that the primary endpoint was met with remdesivir plus standard of care demonstrating superiority in shortening the time to recovery through Day 29 compared with placebo plus standard of care. In the final Day 29 results, patients receiving remdesivir (n = 541) achieved clinical recovery five days faster than those receiving placebo, with a median time to recovery of 10 days with remdesivir and 15 days with placebo and an increased recovery rate by 29% compared with placebo (rate ratio for recovery, 1.29; 95% confidence interval [CI], 1.12 to 1.49; p<0.001). In patients who required oxygen support at baseline (n = 957)patients receiving remdesivir achieved clinical recovery seven days faster than those receiving placebo, with a median time to recovery of 11 days with remdesivir and 18 days with placebo (rate ratio for recovery, 1.31; 95% CI, 1.12 to 1.52). Patients receiving remdesivir demonstrated a 50% more likelihood to have improved by Day 15 compared with those receiving placebo (OR, 1.5; 95% CI, 1.2 to 1.9), and the effect was maintained through Day 29. Also, reduction in disease progression was observed in patients with oxygen requirement. This resulted in low incidence of new mechanical ventilation or ECMO (13% vs. 23%; 95% CI, -15 to -4). The benefit of remdesivir was found to be greater when given within 10 days of symptom onset. In the overall study population, a trend towards reduced mortality at Day 15 (6.7% vs. 11.9%; HR, 0.55; 95% CI, 0.36 to 0.83) and Day 29 (11.4% vs. 15.2%, HR 0.73; 95% CI, 0.52 to 1.03) was observed in remdesivir -treated patients compared with placebo [26] [91] . Earlier reported results from the trial demonstrated that administration of remdesivir statistically and significantly improved clinical odds at day 15 as compared to placebo group. The time for recovery as well as odds of improvement at day 15 were favourable for remdesivir group and consistent with overall study results [30] . Earlier results demonstrated that patients treated with remdesivir recovered after about 10 days, compared with 15 days for patients given placebo. In patients with mild to moderate disease this effect was not observed, where time to recovery was 5 days for both the remdesivir group and the placebo group. Approximately 90% of the study population constituted patients with severe disease, where in time to recovery was 12 days in the remdesivir group and 18 days in the placebo group. However, no difference was observed in time to recovery in patients who started remdesivir when they were already on mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Data on the proportion of patients who died up to 28 days after starting treatment are currently being collected for final analysis. Initial preliminary results from the trial showed that treatment with remdesivir exhibited 31% of recovery from hospitalised patients (n = 1063) than those who received the placebo and suggested a survival benefit with mortality rate of 8.0% for the remdesivir group versus 11.6% for the placebo group [43] [92] [93] .
Updated results from phase III SIMPLE-moderate trial demonstrated that treatment with remdesivir improved COVID-19 symptoms statistically and significantly at day 5 compared to day 11 as compared to standard of care. The odds of improvement with the day 10 treatment group when compared to those receiving only standard of care were numerically favourable, but not statistically significantly different. The mortality reported was less than or equal to 2 percent in all treatment groups [30] . Earlier data from the trial showed greater clinical benefit in higher number of patients than 10 days regimen. In the 5-day treatment group, 76% (146/191) of patients achieved clinical improvement at Day 11, showing statistical significance for a ≥ 1-point improvement in ordinal scale compared with 66% (132/200) of patients in the standard of care alone, (p = 0.026). In the 10-day treatment group, 70% (135/193) of patients achieved clinical improvement at Day 11. In the 5-day and 10 day treatment group, 70% (134/191) and 65% (26/193) of patients showed a ≥ 2-point improvement in ordinal scale at Day 11 compared with 61% (121/200) of patients in the standard of care alone. Number of patients who required oxygen support in 5-day, 10-day and SoC treatment group were 12, 13 and 22, respectively. No patient was died due to worsening disease in 5-day course treatment whereas 2 and 4 patients were died in 10-day and SoC treatment group. Patients with moderate disease who received the 5-day remdesivir plus standard-of-care treatment were 65% more likely to have clinical improvement at Day 11 compared with those in the standard of care group as assessed by a 7-point ordinal score (OR 1.65 [95% CI 1.09-2.48]; p=0.017). The odds of improvement in clinical condition with the 10-day treatment course of remdesivir versus standard of care also showed trend toward improvement but not reaching statistical significance (OR 1.31 [95% CI 0.88-1.95]; p=0.18) [84] [90] .
Interim results of the randomised, controlled, double blind phase III CAP-China remdesivir 1 trial demonstrated that remdesivir for up to 5 days was superior to standard of care (SoC) in improving the clinical status by day 11 in patients (n = 584) with mild or moderate COVID-2019 infections. By day 11, two-point improvement on the ordinal scale occurred in 70% of patients in the 5 day remdesivir arm, 65% in the 10 day remdesivir arm, and 61% in the SoC arm. Patients in the 5 day remdesivir arm were significantly more likely to have an improvement in clinical status than those receiving SoC (odds ratio [OR], 1.65; 95% confidence interval [CI]: 1.09-2.48; p = 0.017). The OR of improvement for the 10 day remdesivir arm compared to SoC was 1.31 (95% CI: 0.88-1.95]; p = 0.183). This improvement in the 5 day remdesivir arm over the SOC arm was noted from day 6 through day 11. A peak of discharge corresponding with the assigned treatment duration of remdesivir was observed, with increased discharges at day 6 in the 5 day remdesivir arm and at day 11 in the 10 day remdesivir arm. A worsening of clinical status of ≥ 1 point in the ordinal scale was observed more commonly in the SoC am (n = 19, 10%) versus the 5 day remdesivir (n = 7, 4%) and 10 day remdesivir (n = 9, 5%) arms [98] [97] .
New results of the phase III PINETREE trial that compared the efficacy and safety of 3 days of intravenously administered remedesivir to standard of care in non-hospitalized, high-risk participants with confirmed COVID-19 showed that baseline demographics and characteristics were balanced across arms with 562 patients undergoing randomization. Overall, 52% were male, 44% were Hispanic/Latino ethnicity and 30% were 60 years old. Median baseline SARS-CoV-2 RNA nasopharyngeal viral load was 6.2 log mL. Treatment with remedesivir significantly reduced COVID-19 hospitalization or all-cause death by day 28 (HR, 0.13; 95% CI, 0.03 – 0.59; p = 0.008) compared to placebo. Participants receiving remedesivir also had significantly lower risk for COVID-19 related medically attended visits or all-cause death by day 28 compared to placebo (HR, 0.19; 95% CI, 0.07 – 0.56; p = 0.0021). In addition, there was no difference between arms in time-weighted average change in nasopharyngeal viral loads from baseline up to day 7 [69] . Earlier data from the phase III PINETREE trial showed that, remedesivir inhibited the ability of the SARS-CoV-2 virus to reproduce itself and effective at preventing severe illness from COVID when given early in the symptom course. Early in the symptom course to moderate and high-risk patients, remdesivir reduced the risk of requiring hospitalization by 87%. A total of 2 of 279 patients (0.7%) in the remdesivir group and 15 of 283 (5.3%) in the placebo group had a Covid-19–related hospitalization by day 28. All Covid-19–related hospitalizations occurred by day 14. No patients in either group died by day 28. The risk of Covid-19–related hospitalization or death from any cause by day 28 was 87% lower in the remdesivir group than in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P=0.008). In prespecified subgroup analyses, the incidence of a primary efficacy end-point event was lower in the remdesivir group than in the placebo group. The incidence of Covid-19–related medically attended visits or death from any cause by day 28 was also lower in the remdesivir group than in the placebo group: 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a medically attended visit (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). By day 14, a total of 2 of 246 patients (0.8%) in the remdesivir group and 20 of 252 (7.9%) in the placebo group had a medically attended visit (hazard ratio, 0.10; 95% CI, 0.02 to 0.43). A total of 5 of 279 patients (1.8%) in the remdesivir group and 18 of 283 (6.4%) in the placebo group were hospitalized for any reason by day 28. Results of a post hoc analysis showed a 72% lower risk of hospitalization for any cause by day 28 in the remdesivir group than in the placebo group (hazard ratio, 0.28; 95% CI, 0.10 to 0.75). Of the 126 patients who completed the baseline FLU-PRO Plus questionnaire before the first infusion, 23 of 66 patients (34.8%) in the remdesivir group and 15 of 60 (25.0%) in the placebo group reported alleviation of symptoms by day 14 (rate ratio, 1.41; 95% CI, 0.73 to 2.69) (Fig. S2A). In a post hoc analysis involving patients who completed the baseline questionnaire any time on the day of the first infusion (either before or after the infusion), 61 of 169 patients (36.1%) in the remdesivir group and 33 of 165 (20.0%) in the placebo group reported alleviation of symptoms by day 14 (rate ratio, 1.92; 95% CI, 1.26 to 2.94) [70] [71] [73] .
Results from the phase II/III SOLIDARITY trial demonstrated a statistically significant 17% lower relative risk of death or progression to needing ventilation in patients requiring supplemental oxygen at baseline, compared to standard of care (RR: 0.83; 95% CI: 0.75–0.93). Additionally a statistically significant 13% lower relative risk of mortality with remdesivir treatment for those patients hospitalized on supplemental oxygen and not requiring mechanical ventilation, compared with standard of care (RR: 0.87; 95% CI: 0.76–0.99). Remdesivir had no significant effect on patients with COVID-19 who were already being ventilated [51]
In Updated results from the phase II/III CARVAN trial, treatment with remdesivir demonstrated the clinical improvement and recovery. In the study, 75% and 85% showed clinical improvement (=2 point increase on the ordinal scale) at day 10 and last assessment, respectively, while 60% and 83% were discharged by day 10 and day 30, respectively [105] . Earlier results showed clinical outcomes including improvement on a 7-point ordinal scale, time to discharge, and oxygenation modality. Clinical improvement based on the clinical ordinal scale and the recovery rate was 83% at last assessment (N=53). Earlier, results from phase II/III CARAVAN trial of remdesivir (RDV) in hospitalized pediatric patients with PCR-confirmed COVID-19 showed that among pediatric patients aged 2m to 17y, 70% had clinical improvement. By last assessment, 8% required supplemental oxygen, all of whom were invasively ventilated. Time to confirmed negative SARS-CoV-2 PCR CoV-2 PCR was 5 and 7 days from nasal/oropharyngeal samples in cohort 2 and 3, respectively, and not estimable in the other cohorts. Median number of RDV doses was 5. At baseline, 67% required supplemental oxygen, including 22% on invasive ventilation; at Day 10, the values were 26% and 15%, respectively. In total, 70% showed clinical improvement on the 7-point ordinal scale at Day 10 [103] [102] [101] [104]
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 28 Feb 2021 | Trial Update | Gilead Sciences plans a phase III trial for COVID-2019 infections (In children, In adolescents, In adults, In the elderly, Combination therapy) in February 2021 (NCT04745351) (EudraCT2020-005416-22) | 23 Mar 2021 |
| 02 Nov 2020 | Trial Update | Gilead Sciences plans a phase I pharmacokinetic trial in New Zealand, Germany, USA and Puerto Rico (IV, infusion) in November 2020 (ACTRN12620001048976p) (700328720) | 01 Nov 2021 |
| 30 Sep 2020 | Trial Update | Gilead Sciences plans a phase III trial for COVID-2019 infections (Early-stage disease) in September 2020 (NCT04501952) (EudraCT2020-003510-12) (700326333) | 29 Sep 2020 |
| 30 Sep 2020 | Trial Update | Gilead Sciences plans a phase I/II trial for COVID-2019 infections (Early-stage disease) in September 2020 (Inhalation,Aerosol) (NCT04539262) (700327349) | 29 Sep 2020 |
| 31 Aug 2020 | Regulatory Status | Gilead Sciences plans to launch remdesivir in the EU on emergency use basis in August 2020 [139] | 04 Aug 2020 |
| 30 Jun 2020 | Trial Update | Gilead Sciences plans the phase II/III CARAVAN trial for COVID-2019 infections (In neonates, In infants, In children, In adolescents) (IV) in June 2020 (NCT04431453) (700323291) | 29 Jul 2020 |
| 31 Mar 2020 | Trial Update | Institut National de la Santé et de la Recherche Médicale (INSERM) plans the phase III DisCoVeRy trial for COVID-2019 infections in France (IV, Infusion), in March 2020 (700320029), (NCT04315948) | 15 Apr 2020 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 11 Oct 2023 | Scientific Update | Efficacy data from a phase III REDPINE trial in Covid-19 infections presented at the IDWeek 2023 (IDW-2023) [62] Updated 07 Feb 2024 |
| 11 Oct 2023 | Scientific Update | Pooled adverse events data from a phase III ACTT-1 trial, phase III PINETREE trial, phase III REDPINE trial presented at the IDWeek 2023 (IDW-2023) [59] Updated 07 Feb 2024 |
| 19 Sep 2023 | Regulatory Status | European Medicines Agency (EMA) grants positive opinion to extend the use of remdesivir to treat people with COVID-2019 infections (with mild to severe hepatic impairment) [18] Updated 21 Sep 2023 |
| 28 Aug 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in COVID-2019-infections(Combination therapy, In volunteers) in USA (Inhalation) Updated 28 Aug 2023 |
| 28 Aug 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Neurological-disorders(Combination therapy, In volunteers) in USA (Inhalation) Updated 28 Aug 2023 |
| 28 Aug 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Neurological-disorders(Monotherapy, In volunteers) in USA (Inhalation) Updated 28 Aug 2023 |
| 24 Aug 2023 | Regulatory Status | The US FDA approves sNDA for remdesevir for COVID-2019 infections in patients with mild, moderate, severe hepatic impairment in USA [19] Updated 30 Aug 2023 |
| 03 Aug 2023 | Regulatory Status | Veklury receives US FDA and EC approval to extend the use of Veklury to treat COVID-19 in people with severe renal impairment, including those on dialysis [20] Updated 18 Aug 2023 |
| 14 Jul 2023 | Regulatory Status | The US FDA approves sNDA for remdesevir for COVID-2019 infections in patients with severe renal impairment in USA [21] Updated 18 Jul 2023 |
| 26 May 2023 | Regulatory Status | CHMP adopts positive opinion to extend the use of remdesivir in COVID-2019 patients with severe renal impairment, including those on dialysis [36] Updated 16 Jun 2023 |
| 28 Apr 2023 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in COVID-2019-infections in Israel (IV, Infusion) Updated 16 Jun 2023 |
| 19 Feb 2023 | Scientific Update | Pharmacokinetics and adverse event data from the phase III REDPINE trial in COVID-2019 infections presented at the 30th Conference on Retroviruses and Opportunistic Infections (CORI-2023) [61] Updated 10 Apr 2023 |
| 10 Feb 2023 | Trial Update | Gilead Sciences completes a phase II/III trial in COVID-2019 infections (In adolescents, In children, In infants, In neonates, In adults) in United Kingdom (IV) (EudraCT2020-001803-17) (NCT04431453) Updated 16 Jun 2023 |
| 07 Nov 2022 | Trial Update | NeuroRx in collaboration with National Institute of Allergy and Infectious Diseases, University of Copenhagen, Medical Research Council, Kirby Institute, National Heart, Lung, and Blood Institute, Cardiothoracic Surgical Trials Network, and Gilead Sciences completes the phase III TESICO trial for COVID-19 respiratory infection and SARS-COV-2 acute respiratory disease (Monotherapy, Combination therapy) in USA (IV) (NCT04843761) Updated 28 Dec 2022 |
| 25 Sep 2022 | Scientific Update | Pharmacokinetics data from a phase I/II CARAVAN trial in Covid-2019 infections presented at the Annual Meeting of the American College of Clinical Pharmacology (ACCP-2022) [106] Updated 08 Nov 2022 |
| 25 Sep 2022 | Scientific Update | Pharmacokinetics data from a phase I trial in Covid-2019 infections presented at the 2022 American College of Clinical Pharmacology Annual Meeting (ACCP-2022) [134] Updated 07 Nov 2022 |
| 16 Sep 2022 | Phase Change - Preregistration | Preregistration for COVID-2019 infections (In children, In infants, In neonates) in European Union (IV) [37] Updated 21 Sep 2022 |
| 15 Sep 2022 | Regulatory Status | WHO recommends the use of Remdesivir for COVID-2019 infections [51] Updated 19 Sep 2022 |
| 15 Sep 2022 | Scientific Update | Efficacy data from the phase II/III SOLIDARITY trial in COVID-2019 infections released by Gilead Sciences [51] Updated 19 Sep 2022 |
| 24 Jul 2022 | Regulatory Status | Committee for Medicinal Products for Human Use (CHMP) adopts a positive opinion recommending full approval of remdesivir for COVID-2019 infections [38] Updated 29 Jul 2022 |
| 19 Jul 2022 | Licensing Status | Gilead Sciences signs joint procurement agreement with the European Commission for remdesivir for COVID-2019 infections [7] Updated 26 Jul 2022 |
| 03 Jun 2022 | Trial Update | Gilead Sciences terminates the phase III REDPINE trial in COVID-2019 infections in USA, Brazil, Portugal, South Africa, Spain and United Kingdom due to study enrollment feasibility (IV) (NCT04745351) Updated 17 Jun 2022 |
| 06 May 2022 | Phase Change - Preregistration | Preregistration for COVID-2019 infections (In infants, In adolescents, In neonates, In adults, In the elderly) in Australia (IV) [22] Updated 22 Sep 2022 |
| 06 May 2022 | Phase Change - Registered | Registered for COVID-2019 infections (In adolescents, In the elderly, In infants, In neonates, In adults) in Australia (IV) [22] Updated 22 Sep 2022 |
| 25 Apr 2022 | Regulatory Status | US FDA approves remdesivir in COVID-2019 infections in pediatric patients 28 days of age and older weighing at least 3 kgs [23] Updated 27 Apr 2022 |
| 24 Apr 2022 | Scientific Update | Updated efficacy and safety data from phase II/III CARAVAN trial for COVID-2019 infections at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022) [105] Updated 29 Apr 2022 |
| 12 Feb 2022 | Scientific Update | Adverse events and efficacy data from a phase II/III trial in COVID-19 infections presented at the 29th Conference on Retroviruses and Opportunistic Infections (CROI-2022) [104] Updated 01 Apr 2022 |
| 12 Feb 2022 | Scientific Update | Adverse events and efficacy data from a phase II/III trial in COVID-19 infections presented at the 29th Conference on Retroviruses and Opportunistic Infections (CROI-2022) [103] Updated 15 Feb 2022 |
| 11 Feb 2022 | Scientific Update | Pharmacodynamics data from a preclinical studies in COVID-2019 infections released by Gilead Sciences [122] Updated 15 Feb 2022 |
| 21 Jan 2022 | Regulatory Status | US FDA expands the pediatric Emergency Use Authorization (EUA) of remdesivir in COVID-2019 infections for non-hospitalized pediatric patients younger than 12 years [28] Updated 04 Feb 2022 |
| 21 Jan 2022 | Regulatory Status | US FDA grants expedited approval of a supplemental new drug application (sNDA) for remdesivir for the treatment of COVID-2019 infections for non-hospitalized adult and adolescent patients [28] Updated 25 Jan 2022 |
| 12 Jan 2022 | Biomarker Update | Biomarkers information updated Updated 14 Jan 2022 |
| 22 Dec 2021 | Scientific Update | Safety and efficacy data from the phase III PINETREE trial in COVID-2019 infections released by Intermoutain Healthcare [70] [71] Updated 28 Dec 2021 |
| 21 Dec 2021 | Regulatory Status | European Commission (EC) approves a variation to the Conditional Marketing Authorization for remdesivir in COVID-19 infections [39] Updated 23 Dec 2021 |
| 21 Oct 2021 | Regulatory Status | Gilead Sciences submits sNDA for the treatment of patients with COVID-2019 infections in an outpatient setting [50] Updated 10 Dec 2021 |
| 29 Sep 2021 | Scientific Update | Efficacy and adverse events data from a phase III trial in COVID-2019 infections presented at ID Week 2021 (IDW-2021) [69] Updated 07 Feb 2022 |
| 22 Sep 2021 | Scientific Update | Adverse events and efficacy data from a phase III trial in COVID-2019 infections released by Gilead Sciences [72] Updated 28 Sep 2021 |
| 01 Sep 2021 | Trial Update | Institut National de la Santé Et de la Recherche Médicale (INSERM) discontinues treatment with remdesivir in the phase III DisCoVeRy trial for COVID-2019 infections (Adjunctive treatment) France, Luxembourg, Austria, Belgium, Norway, Ireland, Hungary and Portugal, based on analyses review by both DSMC/DSMB, the Solidarity Executive Group and the DisCoVeRy steering committee, before September 2021 (NCT04315948) Updated 06 Sep 2021 |
| 26 Jul 2021 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections in Australia (IV) (ACTRN12620001048976) Updated 01 Nov 2021 |
| 26 Jul 2021 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections in New Zealand (IV) (ACTRN12620001048976) Updated 01 Nov 2021 |
| 26 Jul 2021 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections in Puerto Rico (IV) (ACTRN12620001048976) Updated 01 Nov 2021 |
| 26 Jul 2021 | Trial Update | Gilead Sciences initiates phase I trial pharmacokinetic trial for COVID-2019 infections in USA (ACTRN12620001048976) Updated 01 Nov 2021 |
| 18 Jun 2021 | Trial Update | Gilead Sciences and WHO terminates the WHO-SOLIDARITY-GERMANY phase II/III trial in COVID-2019 infections (Adjunctive treatment) in Germany (IV, Infusion) (NCT04575064) (EudraCT2020-001549-38) Updated 19 Sep 2022 |
| 25 May 2021 | Company Involvement | NeuroRx has merged with Big Rock Partners to form NRx Pharmaceuticals Updated 31 May 2021 |
| 24 May 2021 | Regulatory Status | The Committee for Medicinal Products for Human Use (CHMP) recommends renewal of conditional marketing authorisation of remdesivir for COVID-2019 infections in European Union [40] Updated 28 May 2021 |
| 20 Apr 2021 | Trial Update | NeuroRx in collaboration with National Institute of Allergy and Infectious Diseases, University of Copenhagen, Medical Research Council, Kirby Institute, National Heart, Lung, and Blood Institute, Cardiothoracic Surgical Trials Network, and Gilead Sciences initiates enrolment in the phase III TESICO trial for COVID-19 respiratory infection and SARS-COV-2 acute respiratory disease (Monotherapy, Combination therapy) in USA (NCT04843761) Updated 28 Apr 2021 |
| 12 Apr 2021 | Trial Update | Gilead Sciences terminates a phase III trial in COVID-2019 infections (In adults, In adolescents, In children, In the elderly, Early-stage disease) in the USA, United Kingdom, Spain, Denmark and Portugal (IV) [68] (NCT04501952) Updated 21 Apr 2021 |
| 06 Apr 2021 | Regulatory Status | The US FDA approves phase III TESICO trial protocol in COVID-2019 infections (Monotherapy, Combination therapy), in the US [57] Updated 09 Apr 2021 |
| 06 Apr 2021 | Trial Update | National Institutes of Health and National Institute of Allergy and Infectious Diseases plans a phase III TESICO trial in COVID-2019 infections (Monotherapy, Combination therapy), in the US and Other countries [57] Updated 09 Apr 2021 |
| 22 Mar 2021 | Trial Update | Gilead Sciences completes a phase I/II trial in COVID-2019 infections (Early-stage disease) in USA (Inhalation) (NCT04539262) Updated 20 Apr 2021 |
| 11 Mar 2021 | Regulatory Status | Roche plans to share REMDACTA trial data with regulatory authorities Updated 12 Mar 2021 |
| 09 Mar 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (In adolescents, In adults, In the elderly) in USA and Portugal (IV) (NCT04745351) (EudraCT2020-005416-22) Updated 23 Mar 2021 |
| 08 Mar 2021 | Active Status Review | CTP push 326271: initiation for NIO-sponsored trial post authorisation of Remdesivir, thus trial (NCT04583969) not added to profile Updated 10 Mar 2021 |
| 06 Mar 2021 | Scientific Update | Efficacy and adverse events data from a phase II/III CARAVAN trial in COVID-2019 infections presented at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [102] Updated 22 Apr 2021 |
| 06 Mar 2021 | Scientific Update | Adverse events data from a phase III trial in COVID-2019 infections presented at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [100] Updated 20 Apr 2021 |
| 09 Feb 2021 | Trial Update | Gilead Sciences plans a phase III trial for COVID-2019 infections (In children, In adolescents, In adults, In the elderly, Combination therapy) in February 2021 (NCT04745351) (EudraCT2020-005416-22) Updated 23 Mar 2021 |
| 04 Feb 2021 | Phase Change - Marketed | Launched for COVID-2019 infections (Adjuvant therapy, Combination therapy) in Egypt (IV) prior to February 2021 (NCT04738045) Updated 04 Mar 2021 |
| 04 Feb 2021 | Phase Change - Marketed | Launched for COVID-2019 infections (Monotherapy, Adjuvant therapy) in Egypt (IV) prior to February 2021(NCT04738045) Updated 04 Mar 2021 |
| 02 Feb 2021 | Trial Update | Daewoong Pharmaceutical initiates enrolment in a phase III trial for COVID-2019 infections (Combination therapy, In adults, In the elderly) in South Korea (IV) (NCT04713176) Updated 11 Mar 2021 |
| 31 Dec 2020 | Patent Information | Gilead Sciences has patent protection for remdesivir in USA and European Union [141] Updated 28 Apr 2021 |
| 16 Nov 2020 | Company Involvement | Upjohn has merged with Mylan to form Viatris Updated 17 Dec 2020 |
| 27 Oct 2020 | Trial Update | BioSig Technologies paused enrollments and halted a phase-II clinical trial in COVID-2019 infections (Combination therapy) in USA (PO) (NCT04410354) [112] Updated 29 Oct 2020 |
| 23 Oct 2020 | Phase Change - Registered | Registered (emergency use authorisation) for COVID-2019 infections (In children) in USA (IV) [24] [29] Updated 17 Dec 2020 |
| 23 Oct 2020 | Phase Change - Marketed | Launched for COVID-2019 infections (In adolescents, In adults) in USA (IV) [24] Updated 27 Oct 2020 |
| 23 Oct 2020 | Regulatory Status | The US FDA revises emergency use authorisation of remdesivir in COVID-19 infections in pediatric patients less than 12 years [29] Updated 27 Oct 2020 |
| 22 Oct 2020 | Phase Change - Registered | Registered for COVID-2019 infections (In adults, In adolescents) in USA (IV) [26] Updated 26 Oct 2020 |
| 22 Oct 2020 | Regulatory Status | The US FDA granted Fast track and priority Review designation to the NDA submitted for remdesivir for COVID-2019 infections requiring hospitalization (In adolescent, In adults) [25] Updated 26 Oct 2020 |
| 21 Oct 2020 | Scientific Update | Adverse event data from a phase III CAP-China remdesivir 1 trial in COVID-2019 infections presented at the IDWeek 2020 (IDW-2020) [99] Updated 10 Dec 2020 |
| 21 Oct 2020 | Scientific Update | Interim efficacy data from a phase III CAP-China remdesivir 1 trial in COVID-2019 infections presented at the IDWeek 2020 (IDW-2020) [98] Updated 10 Dec 2020 |
| 21 Oct 2020 | Scientific Update | Updated efficacy data from the phase III SIMPLE SEVERE clinical trial in COVID-2019 infections presented at the IDWeek 2020 [81] Updated 10 Dec 2020 |
| 21 Oct 2020 | Scientific Update | Updated efficacy data from the phase III SIMPLE SEVERE clinical trial in COVID-2019 infections presented at the IDWeek 2020 [82] Updated 09 Dec 2020 |
| 15 Oct 2020 | Trial Update | Gilead Sciences plans a phase I pharmacokinetic trial in New Zealand, Germany, USA and Puerto Rico (IV, infusion) in November 2020 (ACTRN12620001048976p) Updated 01 Nov 2021 |
| 08 Oct 2020 | Trial Update | University of Minnesota and National Institute of Allergy and Infectious Diseases initiate phase III ITAC trial in COVID-2019 infections in Mexico and USA (IV) [66] (NCT04546581) Updated 26 Oct 2020 |
| 08 Oct 2020 | Scientific Update | Final efficacy data and safety data from the phase III ACTT-1 trial in COVID-19 infections released by Gilead [91] Updated 13 Oct 2020 |
| 08 Oct 2020 | Licensing Status | Gilead Sciences signs Joint Procurement Agreement with the European Commission for remdesivir (Veklury®) for COVID-2019 infections [138] Updated 12 Oct 2020 |
| 02 Oct 2020 | Regulatory Status | The Pharmacovigilance Risk Assessment Committee (PRAC) initiates review of a safety signal for remdesivir in COVID-19 infections [41] Updated 09 Oct 2020 |
| 22 Sep 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (In adults, In adolescents, In children, In the elderly, Early-stage disease) in USA, United Kingdom (IV) (NCT04501952) (EudraCT-2020-003510-12) Updated 29 Sep 2020 |
| 18 Sep 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (In children, In adolescents, In adults, In the elderly, Early-stage disease) in Denmark, Spain and Portugal (IV) (NCT04501952) (EudraCT-2020-003510-12) Updated 15 Jun 2021 |
| 14 Sep 2020 | Phase Change - I/II | Phase-I/II clinical trials in COVID-2019 infections (Early-stage disease) in USA (Inhalation) (NCT04539262) Updated 12 Oct 2020 |
| 04 Sep 2020 | Trial Update | Gilead Sciences plans a phase I/II trial for COVID-2019 infections (Early-stage disease) in September 2020 (Inhalation,Aerosol) (NCT04539262) Updated 29 Sep 2020 |
| 30 Aug 2020 | Regulatory Status | The US FDA expands emergency use authorization of remdesivir in COVID-19 infections [30] Updated 02 Sep 2020 |
| 30 Aug 2020 | Scientific Update | Efficacy data from a phase III ACTT-1 trial in COVID-19 infections released by Gilead [30] Updated 02 Sep 2020 |
| 30 Aug 2020 | Scientific Update | Efficacy data from a phase III SIMPLE trial in COVID-19 infections released by Gilead [30] Updated 02 Sep 2020 |
| 10 Aug 2020 | Trial Update | Gilead Sciences plans a phase III trial for COVID-2019 infections (Early-stage disease) in September 2020 (NCT04501952) (EudraCT2020-003510-12) Updated 29 Sep 2020 |
| 10 Aug 2020 | Regulatory Status | Gilead Sciences completes rolling NDA submission to the US FDA for COVID-2019 infections (In adults) (IV) [27] Updated 12 Aug 2020 |
| 04 Aug 2020 | Trial Update | National Institute of Allergy and Infectious Diseases initiates the phase III ACTT-3 trial for COVID-2019 infections (Combination therapy, In adults, In the elderly) in Japan, Mexico, South Korea and Singapore (NCT04492475) Updated 26 Oct 2020 |
| 04 Aug 2020 | Trial Update | National Institute of Allergy and Infectious Diseases initiates enrolment in the phase III ACTT-3 trial for COVID-2019 infections (Combination therapy, In adults, In the elderly) in USA (NCT04492475) Updated 17 Aug 2020 |
| 04 Aug 2020 | Phase Change - II | QuantumLeap Healthcare Collaborative initiates a phase II clinical trials in COVID-2019 infections (Combination therapy) in USA (IV) [111] (NCT04488081) Updated 07 Aug 2020 |
| 31 Jul 2020 | Trial Update | National Institute of Allergy and Infectious Diseases completes phase III ACTT-2 trial in COVID-2019 infections (Combination therapy) in USA, United Kingdom, Spain, Singapore, Mexico, South Korea, Denmark, Japan (PO) (NCT04401579) Updated 20 Feb 2023 |
| 29 Jul 2020 | Regulatory Status | Gilead Sciences plans to launch remdesivir in the EU on emergency use basis in August 2020 [139] Updated 04 Aug 2020 |
| 23 Jul 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections (In adolescents, In children, In infants, In neonates, In adults) in United Kingdom (IV) (EudraCT2020-001803-17) (NCT04431453) Updated 29 Jul 2020 |
| 23 Jul 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections (In adolescents, In children, In infants, In neonates, In adults) in USA (IV) (NCT04431453) (EudraCT2020-001803-17) Updated 29 Jul 2020 |
| 21 Jul 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections (In neonates, In infants, In children, In adolescents, In adults) in Spain, Italy (IV) after July 2020 (NCT04431453) (EudraCT2020-001803-17) Updated 10 Dec 2020 |
| 21 Jul 2020 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections (In volunteers, Combination therapy) in USA (Inhalation) (NCT04480333) Updated 24 Jul 2020 |
| 21 Jul 2020 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections (In volunteers, Monotherapy) in USA (Inhalation) (NCT04480333) Updated 24 Jul 2020 |
| 21 Jul 2020 | Phase Change - I | Phase-I clinical trials in Neurological disorders (In volunteers, Combination therapy) in USA (Inhalation) (NCT04480333) Updated 24 Jul 2020 |
| 21 Jul 2020 | Phase Change - I | Phase-I clinical trials in Neurological disorders (In volunteers, Monotherapy) in USA (Inhalation) (NCT04480333) Updated 24 Jul 2020 |
| 13 Jul 2020 | Scientific Update | Efficacy and adverse event data from a compassionate use programme in COVID-2019 infections released by Gilead Sciences [83] Updated 14 Jul 2020 |
| 13 Jul 2020 | Scientific Update | Efficacy data from the phase III SIMPLE-SEVERE trial in COVID-2019 infection released by Gilead Sciences [83] Updated 14 Jul 2020 |
| 10 Jul 2020 | Phase Change - Preregistration | Preregistration for COVID-2019 infections (In adolescents, In adults, In the elderly) in Australia (IV) [22] Updated 22 Sep 2022 |
| 10 Jul 2020 | Phase Change - Registered | Registered for COVID-2019 infections (In adolescents, In the elderly, In adults) in Australia (IV) [22] Updated 22 Sep 2022 |
| 06 Jul 2020 | Phase Change - Registered | Registered for COVID-2019 infections (In adolescents, In children, In adults) in European Union, Iceland, Norway, Liechtenstein (IV) - conditional marketing authorisation (rolling review) [42] Updated 07 Jul 2020 |
| 03 Jul 2020 | Phase Change - Registered | Registered for COVID-2019 infections in United Arab Emirates (IV) [42] Updated 08 Jul 2020 |
| 30 Jun 2020 | Trial Update | Gilead Sciences completes the phase III SIMPLE MODERATE trial in COVID-2019 infections (Adjunctive treatment) in China, France, Germany, Hong Kong, Italy, Japan, Netherlands, Scotland, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, USA(NCT04292730) Updated 07 Aug 2020 |
| 30 Jun 2020 | Trial Update | Gilead Sciences completes a phase-III SIMPLE SEVERE clinical trial in COVID-2019 infections (Adjunctive treatment) in China, France, Germany, Hong Kong, Italy, Japan, Netherlands, Scotland, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, USA (IV) (NCT04292899) Updated 06 Aug 2020 |
| 29 Jun 2020 | Trial Update | Gilead Sciences and WHO initiate phase II/III trial in COVID-2019 infections (Adjunctive treatment) in Germany (IV, Infusion) (NCT04575064) Updated 27 Jan 2021 |
| 29 Jun 2020 | Trial Update | INSERM initiates enrolment in the phase III Discovery trial for COVID-2019 infections in France , Portugal (NCT04315948) Updated 29 Jun 2020 |
| 25 Jun 2020 | Regulatory Status | The Committee for Medicinal Products for Human Use (CHMP) adopts a positive opinion for conditional marketing authorisation (CMA) of remdesivir for the treatment of COVID-2019 infections [43] Updated 29 Jun 2020 |
| 25 Jun 2020 | Scientific Update | Efficacy data from the phase III trial in COVID-2019 infections released by European Medicines Agency [43] Updated 29 Jun 2020 |
| 16 Jun 2020 | Trial Update | Gilead Sciences plans the phase II/III CARAVAN trial for COVID-2019 infections (In neonates, In infants, In children, In adolescents) (IV) in June 2020 (NCT04431453) Updated 29 Jul 2020 |
| 16 Jun 2020 | Phase Change - II | Phase-II clinical trials in COVID-2019 infections (Combination therapy) in USA (IV) (NCT04410354) [113] Updated 24 Jun 2020 |
| 15 Jun 2020 | Licensing Status | Gilead Sciences and Zydus Cadila enter into a non-exclusive licensing agreement to manufacture and distribute remdesivir for COVID-2019 infections [13] Updated 22 Jun 2020 |
| 13 Jun 2020 | Licensing Status | Gilead Sciences enters into a licensing agreement with Dr Reddy’s Laboratories to market remdesivir for COVID-2019 infections [12] Updated 17 Jun 2020 |
| 10 Jun 2020 | Phase Change - Preregistration | Preregistration for COVID-2019 infections (Adjunctive treatment) in Taiwan (IV) before June 2020 Updated 16 Jun 2020 |
| 10 Jun 2020 | Phase Change - Registered | Registered for COVID-2019 infections (Adjunctive treatment) in Singapore (IV) - conditional approval [47] Updated 16 Jun 2020 |
| 10 Jun 2020 | Phase Change - Registered | Registered for COVID-2019 infections (Adjunctive treatment) in Taiwan (IV) - conditional approval [48] Updated 16 Jun 2020 |
| 08 Jun 2020 | Regulatory Status | The EMA receives application for conditional marketing authorisation (CMA) of remdesivir for COVID-2019 infections [44] Updated 29 Jun 2020 |
| 08 Jun 2020 | Regulatory Status | The Paediatric Committee (PDCO) of EMA issues opinion on the paediatric investigation plan (PIP) for remdesivir in COVID-2019 infections before June 2020 [44] Updated 11 Jun 2020 |
| 01 Jun 2020 | Phase Change - Registered | Registered (Restricted emergency use) for COVID-2019 infections (In adults, In adolescents, In children) in India (IV) Updated 14 Oct 2020 |
| 01 Jun 2020 | Scientific Update | Efficacy and adverse events data from the phase III SIMPLE-moderate trial in COVID-2019 infection released by Gilead Sciences [84] Updated 06 Jun 2020 |
| 29 May 2020 | Regulatory Status | Taiwan Food and Drug Administration holds a meeting with pharmaceutical and clinical experts to discuss the application and approval requirements of remdesivir for COVID-2019 infections [48] Updated 16 Jun 2020 |
| 28 May 2020 | Phase Change - III | Phase-III clinical trials in COVID-19 pneumonia(Combination therapy) in Spain, Canada, Brazil, USA and Russia (IV) [77] (NCT04409262) Updated 03 Jun 2020 |
| 22 May 2020 | Phase Change - Preregistration | Preregistration for COVID-2019 infections (Adjunctive treatment) in Singapore (IV), before May 2020 [47] Updated 16 Jun 2020 |
| 22 May 2020 | Trial Update | Gilead Sciences plans clinical trials for remdesivir (Combination therapy) in COVID-2019 infections [86] Updated 01 Jun 2020 |
| 21 May 2020 | Trial Update | National Institute of Allergy and Infectious Diseases completes the phase III (ACTT) trial in COVID-2019 infections in USA, Denmark, Germany, Greece, South Korea, Japan, Mexico, Singapore, Spain and United Kingdom (NCT04280705) Updated 16 Jul 2020 |
| 15 May 2020 | Regulatory Status | The Committee for Medicinal Products for Human Use (CHMP) invites Gilead Sciences to submit additional data and a conditional marketing authorisation application for remdesivir in COVID-2019 infections [44] Updated 11 Jun 2020 |
| 13 May 2020 | Licensing Status | Gilead sciences and Hetero enters into licensing agreement to manufacture and distribute remdesivir for COVID-19 infections [15] Updated 19 May 2020 |
| 12 May 2020 | Licensing Status | Gilead Sciences and Cipla enter into a non-exclusive licensing agreement to manufacture and distribute remdesivir for COVID-2019 infections [14] Updated 16 May 2020 |
| 12 May 2020 | Licensing Status | Gilead Sciences and Mylan enters into a non-exclusive licensing agreement to manufacture and distribute remdesivir worldwide for COVID-2019 infections [8] Updated 14 May 2020 |
| 11 May 2020 | Regulatory Status | The Committee for Medicinal Products for Human Use of EMA recommends expanding the compassionate use remdesivir for COVID-2019 infections [124] Updated 15 May 2020 |
| 07 May 2020 | Phase Change - Registered | Registered for COVID-2019 infections (Adjunctive treatment) in Japan - First global approval (exceptional approval pathway) (IV) [49] Updated 18 May 2020 |
| 05 May 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Combination therapy) in USA, USA, Japan, South Korea, Mexico, Singapore (IV)) [96] (NCT04401579) Updated 11 May 2020 |
| 04 May 2020 | Phase Change - Preregistration | Preregistration for COVID-2019 infections (In children, In adults, In adolescents) in European Union (IV) - rolling review by Committee for Medicinal Products for Human Use (CHMP) [45] Updated 05 May 2020 |
| 04 May 2020 | Regulatory Status | Gilead Sciences receives emergency use authorization from the FDA for remdesivir in COVID-19 infections [32] [31] Updated 05 May 2020 |
| 30 Apr 2020 | Scientific Update | Initial primary efficacy data from the phase II ACTT trial in COVID-2019 infections released by EvergreenHealth [92] Updated 06 May 2020 |
| 30 Apr 2020 | Trial Update | Gilead initiated an expanded access programme for COVID-2019 infections in Canada, Germany, Netherlands, Spain, Switzerland (EudraCT2020-001453-49) (NCT04323761) in April 2020 Updated 05 May 2020 |
| 30 Apr 2020 | Regulatory Status | Gilead Sciences discussing with regulatory authorities regarding data on remdesivir for the treatment of COVID-19 infections [88] Updated 04 May 2020 |
| 30 Apr 2020 | Scientific Update | Efficacy and safety data from a phase III SIMPLE trial in COVID-2019 infections released by Gilead Sciences [85] Updated 04 May 2020 |
| 29 Apr 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in Japan, Switzerland (IV) before April 2020 (NCT04292899) Updated 04 May 2020 |
| 15 Apr 2020 | Trial Update | Capital Medical University, Chinese Academy of Medical Sciences and China-Japan Friendship Hospital suspended the phase III trial for COVID-2019 infections in China (IV) (NCT04252664) Updated 10 Dec 2020 |
| 12 Apr 2020 | Scientific Update | Efficacy data from a compassionate use programme in COVID-2019 infections released by Gilead Sciences [128] Updated 17 Apr 2020 |
| 08 Apr 2020 | Phase Change - Preregistration | Preregistration for COVID-2019 infections (In adults) in USA (IV) [27] Updated 12 Aug 2020 |
| 03 Apr 2020 | Regulatory Status | EMA provides recommendations for compassionate use of remdesivir for COVID-2019 infections in European Union [125] Updated 29 Apr 2020 |
| 03 Apr 2020 | Active Status Review | 9289127 - No updates Updated 03 Apr 2020 |
| 31 Mar 2020 | Trial Update | The Health Sciences Authority initiated an early access programme in Singapore for treatment of COVID-2019 infections [47] Updated 16 Jun 2020 |
| 30 Mar 2020 | Trial Update | Oslo University Hospital plans a phase II/III trial for COVID-2019 infections in Norway (IV) (NCT04321616) Updated 30 Mar 2020 |
| 28 Mar 2020 | Trial Update | Gilead Sciences and WHO initiate phase II/III trial in COVID-2019 infections (Adjunctive treatment) in Norway and Sweden (IV, Infusion) (NCT04321616) Updated 27 Jan 2021 |
| 27 Mar 2020 | Phase Change - Clinical | Clinical trials in COVID-2019 infections in Australia, Austria, Belgium, Cyprus, Czech Republic, Denmark, Greece, Greece, Israel; Hungary, Ireland, Poland, Portugal, Romania, Slovakia, Slovenia (IV) - expanded access (NCT04323761) Updated 29 Jun 2020 |
| 27 Mar 2020 | Trial Update | National institute of allergy and infectious diseases initiates a phase II trial for COVID-2019 infections in USA (IV) Updated 01 Apr 2020 |
| 27 Mar 2020 | Trial Update | Gilead initiated an expanded access programme for COVID-19 infections in USA, France, Italy and United Kingdom (NCT04323761) Updated 31 Mar 2020 |
| 25 Mar 2020 | Regulatory Status | The US FDA withdraws the Orphan Drug status of remdesivir for COVID-2019 infections [53] Updated 27 Mar 2020 |
| 23 Mar 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in France (IV) (NCT04292899) Updated 14 Apr 2020 |
| 23 Mar 2020 | Regulatory Status | The US FDA grants Orphan Drug status to remdesivir for COVID-2019 infections [53] [54] Updated 27 Mar 2020 |
| 23 Mar 2020 | Trial Update | Gilead Sciences initiates phase III clinical trials in COVID-2019 infections (Adjunctive treatment) in China, Taiwan, Singapore, South Korea, Hong Kong, USA, Sweden, United Kingdom, Netherlands, Italy, Spain, Germany (IV) before March 2020 (NCT04292730) Updated 24 Mar 2020 |
| 22 Mar 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in Belgium, Norway, Portugal, Ireland, Hungary (IV) (NCT04315948) (EudraCT2020-000936-23) Updated 06 Sep 2021 |
| 22 Mar 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in Austria (IV) (NCT04315948) Updated 29 Jun 2020 |
| 22 Mar 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in Luxembourg (IV, Infusion) (NCT04315948) (EudraCT2020-000936-23) [79] Updated 15 Apr 2020 |
| 20 Mar 2020 | Trial Update | Institut National de la Santé et de la Recherche Médicale (INSERM) plans the phase III DisCoVeRy trial for COVID-2019 infections in France (IV, Infusion), in March 2020 , (NCT04315948) Updated 15 Apr 2020 |
| 18 Mar 2020 | Phase Change - II | Phase-II clinical trials in COVID-2019 infections (Adjunctive treatment) in Canada (IV) (NCT04330690) Updated 29 Jun 2020 |
| 10 Mar 2020 | Trial Update | U.S. Army Medical Research and Development Command initiates an Expanded access programme for COVID-19 infections in USA (NCT04302766) Updated 17 Mar 2020 |
| 06 Mar 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in Taiwan, Singapore, South Korea, Hong Kong, USA, Sweden, United Kingdom, Netherlands, Italy, Spain, and Germany (IV) (NCT04292899) Updated 24 Mar 2020 |
| 01 Mar 2020 | Trial Update | Gilead Sciences initiates a compassionate use programme for COVID-2019 infections in USA, Europe, Canada and Japan, before March 2020 [128] Updated 20 Apr 2020 |
| 01 Mar 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019-infections (Adjunctive treatment) in China (IV) [89] (NCT04292899) Updated 01 Mar 2020 |
| 28 Feb 2020 | Trial Update | Remdesivir is available on a Compassionate basis for the treatment of COVID-2019-infections globally (IV) [89] Updated 02 Mar 2020 |
| 21 Feb 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections in Denmark (IV) (NCT04280705) Updated 26 Jul 2020 |
| 21 Feb 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections in Greece (IV) (NCT04280705) Updated 06 Jul 2020 |
| 21 Feb 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections in Denmark, Germany, Greece, Japan, Mexico, United Kingdom (IV) (NCT04280705) Updated 05 May 2020 |
| 21 Feb 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019-infections in USA, Singapore, South Korea and Spain (IV) (NCT04280705) Updated 27 Feb 2020 |
| 12 Feb 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019-infections in China (IV) (NCT04252664) Updated 10 Dec 2020 |
| 05 Feb 2020 | Trial Update | Capital Medical University plans a phase III trial for COVID-2019-infections (NCT04252664) Updated 13 Feb 2020 |
| 07 Oct 2019 | Trial Update | National Institute of Allergy and Infectious Diseases completes the phase II PREVAIL IV trial for Ebola virus infections in Guinea and Liberia (NCT02818582) Updated 29 Jun 2020 |
| 12 Aug 2019 | Trial Update | Ridgeback Biotherapeutics terminates the phase I/II PALM trial for Ebola virus infections in Congo and USA (IV) (NCT03719586) [130] Updated 14 Aug 2019 |
| 25 Oct 2018 | Phase Change - II | Phase-II clinical trials in Ebola virus infections in Congo (IV) (NCT03719586) Updated 02 Nov 2018 |
| 25 Oct 2018 | Trial Update | Gilead Sciences and National institute of allergy and infectious diseases initiates a phase II trial for Ebola virus infections in USA (IV) (NCT03719586) Updated 02 Nov 2018 |
| 29 Jan 2018 | Other | Chemical structure information added Updated 29 Jan 2018 |
| 28 Jun 2016 | Trial Update | National Institute of Allergy and Infectious Diseases plans the phase II PREVAIL IV trial for Ebola virus infections in Guinea and Liberia (IV) (NCT02818582) Updated 04 Jul 2016 |
| 01 Jun 2016 | Phase Change - II | Phase-II clinical trials in Ebola virus infections in Guinea and Liberia (IV) (NCT02818582) Updated 09 Nov 2016 |
| 01 Dec 2015 | Licensing Status | Gilead Sciences and Ligand Pharmaceuticals enter into supply agreement for Captisol®-enabled remdesivir for Ebola virus infections (Ligand Pharmaceuticals, Form 10-K, December 2015) Updated 28 Feb 2018 |
| 21 Oct 2015 | Regulatory Status | GS 5734 is available on a Compassionate basis for the treatment of Ebola virus infections in United Kingdom [135] Updated 28 Oct 2015 |
| 05 Oct 2015 | Phase Change - I | Phase-I clinical trials in Ebola virus infections in USA (Parenteral) Updated 05 Oct 2015 |
| 05 Oct 2015 | Scientific Update | Preclinical pharmacodynamics data in Ebola virus infections released by Gilead Sciences [136] Updated 05 Oct 2015 |
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The (Norwegian) NOR Solidarity Multicenter Trial on the Efficacy of Different Anti-viral Drugs in SARS-CoV-2 Infected Patients
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A Multi-centre, Adaptive, Randomized, Open-label, Controlled Clinical Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Patients (CATCO: Canadian Treatments for COVID-19), in Conjunction With the Public Health Emergency SOLIDARITY Trial (World Health Organization)
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I-SPY COVID TRIAL: An Adaptive Platform Trial to Reduce Mortality and Ventilator Requirements for Critically Ill Patients
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Members Of The COVID R&D Alliance And Quantum Leap Healthcare Collaborative Enroll First Patients In I-SPY COVID Trial.
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ViralClear halts its Phase 2 Hospitalized COVID-19 Trial.
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ViralClear Opens Enrollment with First Patient Dosing in Phase II Human Trial of Anti-Viral MMPD Oral Solution for Treatment of COVID-19.
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Oral Merimepodib in Combination With Intravenous Remdesivir in Adult Patients With Advanced Coronavirus Disease 2019 (COVID-19)
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A Phase 1b/2a Study in Participants With Early Stage COVID-19 to Evaluate the Safety, Efficacy, and Pharmacokinetics of Remdesivir Administered by Inhalation
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Expanded Access Treatment Protocol: Remdesivir (RDV; GS-5734) for the Treatment of SARS-CoV2 (CoV) Infection
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Prime Healthcare Participating in Program for Promising COVID-19 Treatment.
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Froedtert & the Medical College of Wisconsin Bolster Resources in Fight Against COVID-19 with Study of Remdesivir.
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Under FDA law, approval of a new drug requires substantial evidence of effectiveness and a demonstration of safety for the drug?s intended use(s). The approval of remdesivir (Veklury) for the treatment of patients hospitalized with COVID-19 met this legal and scientific standard. Internet-Doc 2021;.
Available from: URL: https://www.fda.gov/drugs/news-events-human-drugs/remdesivir-veklury-approval-treatment-covid-19-evidence-safety-and-efficacy -
Ligand's Technologies Support and Enable Potential Coronavirus Treatments.
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A phase I, open-label single-dose study analyzing pharmacokinetics of Remdesivir and its metabolites in participants with mild to severe hepatic impairment
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Veklury(Rm) (Remdesivir) Retains Antiviral Activity Against Omicron, Delta and Other Emergent SARS-CoV-2 Variants in Multiple In Vitro Studies.
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A Randomized, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and in Combination With NA-831 in Healthy Volunteers
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EMA recommends expanding remdesivir compassionate use to patients not on mechanical ventilation.
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EMA provides recommendations on compassionate use of remdesivir for COVID-19
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Intermediate-Size Patient Population Expanded Access Treatment Protocol for Coronavirus Disease 2019 (COVID-19) Remdesivir (RDV; GS-5734™)
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Gilead Sciences Announces Fourth Quarter and Full Year 2015 Financial Results.
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Data on 53 Patients Treated With Investigational Antiviral Remdesivir Through the Compassionate Use Program Published in New England Journal of Medicine.
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Compassionate Use Program For the Treating Severely Ill Patients of COVID-19 With Remdesivir
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Ridgeback Biotherapeutics LP announces an update on mAb114, an experimental treatment for Ebola.
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A Multicenter, Multi-Outbreak, Randomized, Controlled Safety and Efficacy Study of Investigational Therapeutics for the Treatment of Patients With Ebola Virus Disease
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PREVAIL IV: Double-Blind, Randomized, Two-Phase, Placebo-Controlled, Phase II Trial of GS-5734 to Assess the Antiviral Activity, Longer-Term Clearance of Ebola Virus, and Safety in Male Ebola Survivors With Evidence of Ebola Virus Persistence in Semen
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A Phase 1 Open-Label, Parallel-Group, Single-Dose Study to Evaluate the Pharmacokinetics of Remdesivir and Metabolites in Participants with Normal Renal Function and Renal Impairment
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Zhang H, Juneja K, Llewellyn J, Kwan A, Davies S, Xiao D, et al. Pharmacokinetics & Safety of Remdesivir in Renal Im- pairment. ACCP-2022 2022; abstr. 083.
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Gilead Provides Update on Investigational Compound, GS-5734, for the Treatment of Ebola Virus Disease.
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Nucleotide prodrug GS-5734 is a broad-spectrum filovirus Inhibitor that provides complete therapeutic protection against the development of Ebola virus disease (EVD) in infected non-human primates. Internet-Doc 2015;.
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An Open Letter from Daniel ODay, Chairman & CEO, Gilead Sciences.
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Gilead Sciences Signs Joint Procurement Agreement With the European Commission for Veklury(RM)(remdesivir).
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European Commission secures EU access to Remdesivir for treatment of COVID-19.
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$6.5 billion in NIH funding for foundational research enabled Emergency Use Authorization of remdesivir for treating COVID-19.
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Gilead Sciences_SEC_Dec 2020. Internet-Doc 2021;.
Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/882095/000088209521000008/gild-20201231.htm -
Jordan R, Hogg A, Warren T, De Wit E, Sheahan T, Lo M, et al. Broad Spectrum Investigational Agent GS-5734 for the Treatment of Ebola, MERS Coronavirus and Other Pathogenic Viral Infections with High Outbreak Potential. IDW-2017 2017; abstr. LB-9.
Available from: URL: https://idsa.confex.com/idsa/2017/webprogram/Paper67515.html -
Phase II Trial of Concurrent, Split Course Chemoradiation Followed by Durvalumab (MEDI4736) in Poor Risk and/or Elderly Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer
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